I've confirmed that CORD10 is the SEMA4A form (OMIM 610283), not PITPNM3, which is CORD5. I'm now getting PMIDs and clinical details for the human reports, then I'll write the report.

Cone-rod dystrophy 10 (CORD10; MONDO:0012464): research report

Scope and caveats

• Tool limits. OMIM, PMC and the JMG full text were blocked in this environment (proxy refusal and a reCAPTCHA page). Details from those sources are therefore taken from search-result summaries, not from the papers themselves.
• No verbatim abstract quotes. I could not retrieve abstract text, so this report has none. Every snippet destined for the KB must be fetched with just fetch-reference and quoted from the cache.
• Source labels. "Verified" means seen in a search result or the MONDO record. "Unverified" means from my memory or not seen in a source.
• Gene identity. My first query tied CORD10 to PITPNM3. That was wrong. PITPNM3 causes CORD5 (OMIM 600977). CORD10 is the SEMA4A form, as shown below.

1. Disease information

Overview. CORD10 is a progressive retinal dystrophy in which cone loss comes first, followed by rod loss. Color vision and acuity decline first, then night blindness and peripheral field loss (OMIM and MalaCards summaries). It is attributed to compound heterozygous SEMA4A variants and is autosomal recessive. This rests on a single 2006 paper.

Identifiers (from the OLS MONDO record, plus search summaries):

MONDO definition: "Any cone-rod dystrophy in which the cause of the disease is a mutation in the SEMA4A gene."

Synonyms: cone-rod dystrophy type 10, CORD10, SEMA4A cone-rod dystrophy, cone-rod dystrophy caused by mutation in SEMA4A.

Allelic phenotype. Retinitis pigmentosa 35 (RP35, OMIM 610282) is also attributed to SEMA4A. Any entry should record the CORD10/RP35 overlap.

Data source. The resources above are aggregated disease-level records. The primary evidence is a small patient cohort (see section 4).

2. Etiology

• Cause. Genetic, from compound heterozygous SEMA4A (semaphorin 4A) variants on 1q22 (OMIM 610283 summary).
• Risk, protective and gene-environment factors. None are documented. I found nothing on modifier genes, protective alleles or exposures.
• Mouse hint. A press summary of the earlier mouse work says Sema4A moves retinoid-binding proteins and retinoids between the cell surface and the endoplasmic reticulum under normal conditions. The same summary mentions oxidative stress. This hints at a gene-environment angle, but it is mouse data only and I did not see the primary text.

3. Phenotypes

Human clinical detail is thin. The 2006 paper reported two CRD patients with biallelic variants. I did not retrieve per-patient data, so frequencies, ages at onset and quality-of-life data are unavailable.

• Course: progressive. Onset ages are not confirmed.
• Do not copy CURIEs from this table. Each must be read from a lookup, per the repo rules.

4. Genetic and molecular information

Gene. SEMA4A is HGNC lowercase form hgnc: plus the ID, which I did not look up. The OMIM gene entry is 607292. The protein is a 760-residue transmembrane semaphorin.

Abid et al. 2006 (J Med Genet 43:378–381, PMID:16199541 per GenCC and DisGeNET): - 190 unrelated patients were screened (search summary). - Two missense variants, p.D345H and p.F350C, were found only in affected people. Both lie in the conserved semaphorin domain, and neither appeared in 100 controls. - OMIM-derived summaries describe compound heterozygosity for two substitutions in two RP and two CRD patients. Three RP patients and one congenitally blind patient carried a single heterozygous change. - p.R713Q was also reported. See the caveats below.

Evidence strength: - A Genomics England panel curator noted biallelic evidence from this one paper (two RP, two CRD patients) and no newer reports. - Australian PanelApp rates SEMA4A Amber for recessive RP and Red for dominant RP. - R713Q is common in gnomAD (more than 10,000 heterozygotes and 299 homozygotes). It did not segregate with disease in PMID:28805479 and is tagged refuted for dominant RP. - Treat the gene-disease link as limited. ClinGen and GenCC classifications should be checked for a tier to copy. I did not retrieve them.

Functional consequence. The F350C change causes abnormal localization of the Sema4A protein. In mice this impairs endosomal sorting (Nojima 2013, see section 6). Whether the human variants act as loss of function is not directly shown. Modifier genes and epigenetic changes are not documented, and no chromosomal abnormalities are described.

5. Environmental information

None documented. There are no known infectious agents, toxins or lifestyle factors.

6. Mechanism and pathophysiology

Ordered causal chain (steps 1–3 mouse-derived, step 4 inferred, step 5 not shown): 1. Biallelic SEMA4A variants, such as F350C, are present in the semaphorin domain (human genetics, PMID:16199541). 2. The mutant protein is mislocalized. In mouse RPE, Sema4A normally regulates endosomal sorting (Nojima 2013, Nat Commun). 3. Sorting of molecules needed for photoreceptor survival and phototransduction is impaired (Nojima 2013, mouse). 4. Photoreceptors degenerate. This is shown for F350C/F350C and Sema4A−/− mice. Its extension to humans is inferred. 5. Cones are affected first and rods later in humans. The mouse data do not establish the human order.

Supporting details: - Cell types and tissue. The mouse work places the mechanism in retinal pigment epithelium and photoreceptors. Suggested CL terms are retinal pigment epithelial cell, retinal cone cell and retinal rod cell. Look up the CURIEs. - Rescue. Sema4A gene transfer prevented photoreceptor degeneration in Sema4AF350C/F350C and Sema4A−/− mice (Nojima 2013). - Suggested GO terms (bind only after lookup): endosomal transport, protein localization to membrane, and visual perception. - Molecular profiling. No transcriptomic, proteomic, single-cell or other omics findings were found.

7. Anatomical structures affected

• Primary: the retina, meaning photoreceptors (cones then rods) and the RPE.
• Systemic involvement: none described.
• Localization: bilateral, as for retinal dystrophies generally. I did not confirm this for CORD10.
• Subcellular: endosomal and cell-surface compartments, per the mouse sorting data.

8. Temporal development

Progressive, with cone symptoms before rod symptoms (OMIM). Age at onset, rate and staging are not retrieved. Remission is not expected.

9. Inheritance and population

• Inheritance: autosomal recessive (compound heterozygous). Genomics England lists both monoallelic and biallelic modes for the gene, but the dominant evidence is weak.
• Prevalence: not reported. It is probably very rare. Orphanet 1872 should be checked for a prevalence class.
• Founder effects, consanguinity and carrier frequency: not documented. Note that R713Q is common in population databases.
• Related locus. PITPNM3 (CORD5) is a separate dominant disease and should not be confused with this one. Its Q626H variant was reported in Swedish families, with a later 163-patient screen suggesting PITPNM3 is an uncommon cause.

10. Diagnostics

I found no CORD10-specific guidance. Standard retinal dystrophy workup applies: - Full-field ERG, expected to show cone responses reduced before or alongside rod responses. This is expected from the disease class, not shown for this gene. - Visual fields, fundus imaging and optical coherence tomography. - Genetic testing through retinal dystrophy gene panels. Genomics England and PanelApp include SEMA4A. - Interpret SEMA4A variants cautiously because the evidence is limited. R713Q alone should not be called pathogenic. - Check GeneReviews with just check-genereviews. I found no chapter for this entity.

11. Outcome and prognosis

Vision loss is progressive. No survival, life-expectancy or quality-of-life data were found. Prognostic factors are unknown.

12. Treatment

• No approved or disease-specific therapy. Management is supportive: low-vision aids, rehabilitation and genetic counseling. Suggested NCIT terms include Supportive Care (NCIT:C15747), Rehabilitation (NCIT:C15315) and Genetic Counseling (NCIT:C15240). These come from the CLAUDE.md list, but verify them before binding.
• Experimental. Sema4A gene transfer prevented degeneration in mice (Nojima 2013). No human trial was found. Search ClinicalTrials.gov before asserting this.

13. Prevention

• Genetic counseling and cascade testing: carrier risk of 25% per sibling given a recessive mode.
• Preimplantation or prenatal testing: possible once biallelic pathogenic variants are established.
• No other prevention measures are known.

14. Other species and natural disease

No naturally occurring disease was identified and I did not check OMIA. Mouse Sema4a is the relevant ortholog.

15. Model organisms

Fidelity. The knock-in directly models the human F350C allele. Whether the mouse recapitulates human cone-first progression is unknown, and the model is apparently homozygous. This fits a HUMAN_MODEL_MISMATCH-style discussion if curated. The Nojima PMID is unresolved: a search summary gave 23360997 but flagged it uncertain, so confirm via just fetch-reference before citing.

Suggested KB handling

• Evidence is thin. Use evidence_source: HUMAN_CLINICAL for Abid 2006 and MODEL_ORGANISM for the mouse papers.
• Gene-disease validity. Run just check-gene-validity and look for ClinGen records. Do not assign a tier yourself.
• Allelic overlap. Mention RP35 (MIM 610282) in the entry notes.

Sources

• MONDO:0012464 via EBI OLS
• OMIM #610283 (seen only in search results)
• Wikidata Q32146111
• MalaCards CORD10
• Abid et al. 2006, J Med Genet 43:378
• Genomics England PanelApp, SEMA4A
• Australian PanelApp, SEMA4A (recessive RP)
• Nojima et al. 2013, Nat Commun
• Rice et al. 2004 record via RIKEN MGI RDF
• Köhn et al. 2007, CORD5/PITPNM3

Reference Validation

Checked with linkml-reference-validator 0.3.0.

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• MONDO:0012464 (5 mentions) - the report calls it "not obsolete"; MONDO calls it cone-rod dystrophy 10