| domain | best-supported finding | evidence type | key citation metadata (author/year/PMID/DOI) | evidence limitation |
|---|---|---|---|---|
| Disease identity | HOXC13-related pure hair-nail ectodermal dysplasia corresponds to ectodermal dysplasia 9 (ECTD9/PHNED), a congenital disorder primarily affecting hair and nails. (pqac-00000000, pqac-00000002, pqac-00000003) | Human clinical genetics | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | Context does not provide MONDO/Orphanet/ICD identifiers; disease nomenclature varies across papers. |
| Core phenotype | The most consistent phenotype is congenital hypotrichosis to complete alopecia with dystrophy of finger- and toenails, while teeth, sweating, skeleton, and nervous system are typically normal. (pqac-00000000, pqac-00000002, pqac-00000003) | Human clinical observations | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | Small number of reported families; severity range across cases is not well quantified. |
| Variant: c.390C>A (p.Tyr130*) | A homozygous nonsense HOXC13 variant c.390C>A (p.Tyr130*) was identified in affected individuals and supports loss of function. (pqac-00000000) | Human molecular genetics | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029 | Family-level evidence; allele frequency and ClinVar classification are not given in context. |
| Variant: 27.6-kb deletion | A homozygous 27.6-kb microdeletion involving HOXC13 exon 1/intron 1 was reported in an affected family, consistent with a null allele. (pqac-00000001) | Human molecular genetics | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029 | Exact HGVS genomic nomenclature beyond coordinates is not fully standardized in the context. |
| Variant: c.812A>G (p.Gln271Arg) | A homozygous missense variant c.812A>G (p.Gln271Arg) in the DNA-binding domain was reported in a North American/Hispanic proband with classic PHNED. (pqac-00000003) | Human clinical genetics | Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | Single-family report; functional assay data are limited in the context to in silico predictions. |
| Variant: c.929A>C (p.Asn310Thr) | A homozygous missense variant c.929A>C (p.Asn310Thr) in the homeobox DNA-binding domain was identified in a consanguineous Pakistani family. (pqac-00000002) | Human clinical genetics + computational structural analysis | Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y | Functional evidence is primarily bioinformatic/modeling in the cited context. |
| Inheritance | Reported human HOXC13-related PHNED cases are best supported as autosomal recessive, often in consanguineous families; heterozygous carriers are generally unaffected in human reports. (pqac-00000000, pqac-00000002, pqac-00000006) | Human pedigree analysis | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Perez et al., 2022, PMID not provided in context, DOI: 10.1111/exd.14469 | Mouse data suggest possible semi-dominant effects for a specific mutant allele, which may not generalize to humans. |
| Mechanism/targets | HOXC13 acts as a transcription factor required for hair/nail differentiation; reported downstream or associated targets include hair keratins (e.g., KRT35, KRT85), FOXN1, DSG4, CRISP1, and FOXQ1, with reduced expression in HOXC13-deficient tissue. (pqac-00000001, pqac-00000002, pqac-00000007) | Human tissue expression, mouse functional studies, in vitro/in silico interpretation | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Perez et al., 2022, PMID not provided in context, DOI: 10.1111/exd.14469 | Direct target status is stronger for some genes than others; pathway map remains incomplete. |
| Model organisms | Hoxc13-deficient or mutant mice show alopecia and nail defects; additional engineered pig and rabbit knockout models recapitulate major hair/nail abnormalities and support conserved function. (pqac-00000005, pqac-00000006, pqac-00000007) | Mouse, pig, rabbit models | Perez et al., 2022, PMID not provided in context, DOI: 10.1111/exd.14469; supporting cited models in Perez et al.: Han et al., 2017, PMID 28011715; Deng et al., 2019, PMID 30125135 | Animal models may show extra phenotypes (e.g., short lifespan, vertebral findings) not typical of reported human disease. |
| Epidemiology | The disorder is ultra-rare and described through a small number of families from multiple ancestries; robust prevalence or incidence estimates are not available in the retrieved evidence. (pqac-00000000, pqac-00000002, pqac-00000003) | Aggregated inference from case reports | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | No population-based registries or denominator-based studies were identified in context. |
| Diagnostics | Diagnosis is primarily clinical suspicion based on congenital hair/nail findings followed by confirmatory genetic testing of HOXC13; sequencing and deletion analysis are both relevant because both SNVs and a multi-kb deletion have been reported. (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003) | Human diagnostic genetics | Lin et al., 2012, PMID 23063621, DOI: 10.1016/j.ajhg.2012.08.029; Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | No disease-specific formal diagnostic guideline or validated biomarker beyond genotype was identified. |
| Treatment/trial status | No disease-modifying therapy or disease-specific interventional clinical trial was identified in the retrieved evidence; management appears supportive/cosmetic and genetics-based counseling is relevant. (pqac-00000002, pqac-00000003) | Evidence gap from literature/trial search | Khan et al., 2017, PMID 28403827, DOI: 10.1186/s12881-017-0402-y; Li et al., 2017, PMID not provided in context, DOI: 10.1111/pde.13074 | Absence of evidence is not proof of absence globally; no trial identifiers were available in context. |


*Table: This table summarizes the strongest available evidence for HOXC13-related pure hair-nail ectodermal dysplasia across disease definition, variants, mechanism, models, diagnostics, and treatment gaps. It is designed as a compact reference for building a disease knowledge base entry without overstating unavailable epidemiology or therapeutic evidence.*