| Gene | 18p location (hg19, as reported) | Core function | Haploinsufficiency / dosage status in review | Phenotypes linked to hemizygosity or conditional hemizygosity | Inheritance / mechanistic model | Key evidence from Hasi-Zogaj 2015 review |
|---|---|---|---|---|---|---|
| CETN1 | 580,369-581,524 | Centrin family protein involved in centrosome position/segregation and microtubule functions | Not established as pathogenic for a human 18p- phenotype; discussed as a candidate dosage-sensitive gene | No specific confirmed human phenotype from 18p hemizygosity; possible relevance to male fertility considered but unproven | Unclear; no direct phenotype established in 18p-; maternal transmissions including this region argue against female infertility | Review notes mouse heterozygous mutations cause infertility, but human 18p deletions including CETN1 have been maternally transmitted; no firm human dosage phenotype assigned (pqac-00000005) |
| TGIF1 | 3,451,591-3,458,406 | Homeodomain transcriptional regulator in TGF-beta/NODAL-related developmental signaling | Likely dosage-sensitive / haploinsufficient | Holoprosencephaly (HPE), HPE microforms, single central incisor, midline/pituitary anomalies | Classic haploinsufficiency with incomplete penetrance; phenotype modified by additional factors | In the review cohort, 11% (6/65) of individuals hemizygous for TGIF1 had HPE-spectrum malformations; TGIF1 point mutations are established in HPE and 18p hemizygosity is a recognized risk factor (pqac-00000005, pqac-00000003) |
| DLGAP1 | 3,499,183-3,880,068 | Postsynaptic density scaffold protein | Candidate dosage-sensitive / possible risk gene | Autism spectrum disorder / autistic features | Risk-factor model rather than fully penetrant haploinsufficiency | Seven of eight individuals with clinically significant autism scores had deletions including DLGAP1; proposed because of postsynaptic density enrichment (pqac-00000006, pqac-00000007) |
| TWSG1 | 9,334,765-9,402,418 | BMP-binding extracellular developmental regulator involved in dorsal-ventral patterning and craniofacial development | Conditional / uncertain dosage sensitivity | Possible modifier for HPE; possible contribution to dental/caries phenotype; direct role in 18p HPE not proven | Likely modifier-gene model, potentially interacting with TGIF1 or environmental exposures | Review states evidence for direct involvement in HPE is conflicting; no study participant with isolated TWSG1 hemizygosity had HPE, though prior literature suggested combined deletion with TGIF1 may increase HPE penetrance (pqac-00000006, pqac-00000012) |
| ANKRD12 | 9,136,751-9,285,983 | Ankyrin repeat domain-containing protein; exact dosage mechanism uncertain | Candidate conditional dosage-sensitive / risk gene | Autism spectrum disorder risk | Risk-factor model | Listed among 18p genes implicated by overlap in individuals with clinically significant autism scores (pqac-00000007) |
| LAMA1 | 6,941,743-7,117,813 | Laminin alpha-1, basement membrane component | Likely dosage-sensitive / conditional | Retinal vascular anomalies, keratosis pilaris / ulerythema ophryogenes candidate, possible ocular/cerebellar features | Incomplete penetrance; possible revealed recessive-allele model for severe manifestations | In the cohort, 1/32 with LAMA1 hemizygosity had tortuous anomalous retinal vessels; skin findings were common but nonspecific; review discusses relevance based on known recessive LAMA1 disease and mouse retinal vasculopathy (pqac-00000003) |
| LRRC30 | 7,231,137-7,232,042 | Leucine-rich repeat-containing protein; function poorly defined | Candidate conditional dosage-sensitive / risk gene | Autism spectrum disorder risk | Risk-factor model | Included among genes recurrently deleted in individuals with autism-range GARS/GARS-2 scores (pqac-00000007) |
| GNAL | 11,689,014-11,885,683 | G-protein alpha-olf subunit involved in receptor signaling | Likely dosage-sensitive / conditional | Dystonia, torsion dystonia, movement disorders | Conditional / incompletely penetrant haploinsufficiency | GNAL is a major adult-onset dystonia gene in the literature; in the 18p- cohort, 2/58 individuals with deletions encompassing GNAL had dystonia, supporting low-penetrance risk from hemizygosity (pqac-00000003) |
| IMPA2 | 11,981,427-12,030,885 | Inositol monophosphatase-related function | Candidate conditional dosage-sensitive / risk gene | Autism spectrum disorder risk | Risk-factor model | Seven of eight autism-range cases had deletions including DLGAP1/LRRC30/ANKRD12/IMPA2; one additional case lacked IMPA2, suggesting it may contribute but is not solely causal (pqac-00000006, pqac-00000007) |
| AFG3L2 | 12,328,943-12,377,275 | Mitochondrial protease subunit involved in protein quality control and ribosome assembly | Conditional dosage-sensitive | Spinocerebellar ataxia type 28 (SCA28)-like risk; possible later-onset ataxia | Conditional haploinsufficiency / age-dependent penetrance | None of 15 examined individuals met diagnostic criteria for SCA28, but point mutations in AFG3L2 cause dominant ataxia and the review highlights possible future age-related manifestation in 18p- adults (pqac-00000003, pqac-00000008) |
| PTPN2 | 12,792,301-12,884,334 | Protein tyrosine phosphatase involved in immune regulation | Conditional dosage-sensitive / susceptibility gene | Autoimmune disease risk (juvenile rheumatoid arthritis, thyroid autoimmunity, celiac disease, vitiligo, psoriasis, alopecia, Sjogren syndrome) | Susceptibility / second-hit model | No inflammatory bowel disease was seen in 67 hemizygous individuals, but 11 had autoimmune conditions; the review considers PTPN2 a plausible contributor with incomplete penetrance and likely additional modifiers (pqac-00000007) |
| SMCHD1 | 2,655,886-2,805,015 | Structural maintenance of chromosomes hinge domain protein; chromatin repression and methylation including D4Z4 | Conditional dosage-sensitive | Risk for facioscapulohumeral muscular dystrophy type 2 (FSHD2), retinal vasculopathy in susceptible background | Digenic / permissive-background model requiring hemizygosity plus permissive D4Z4 allele and repeat context | Review states SMCHD1 hemizygosity alone is insufficient, but individuals with 18p deletion may be at risk for FSHD when a permissive 4q D4Z4 background is present; this was later directly supported by Balog et al. 2018 (pqac-00000007, pqac-00000010) |
| PTPRM | Not specified in the review pages provided | Receptor-type protein tyrosine phosphatase | Not classified in Hasi-Zogaj 2015 as a key dosage-sensitive gene | No specific phenotype assigned in the review | Unclear | Mentioned in later case literature on 18p autoimmunity, but not among the key mapped dosage-sensitive genes in the Hasi-Zogaj review sections provided (pqac-00000009) |
| ADCYAP1 | Not specified in the review pages provided | Pituitary adenylate cyclase-activating polypeptide signaling | Not classified in Hasi-Zogaj 2015 as a key dosage-sensitive gene | No specific phenotype assigned in the review | Unclear | Reported in later case literature as a potentially relevant deleted gene in autoimmune endocrinopathy, but not a mapped key dosage-sensitive gene in the review (pqac-00000009) |
| LPIN2 | Not specified in the review pages provided | Lipin-2, lipid metabolism/inflammation-related protein | Not classified in Hasi-Zogaj 2015 as a key dosage-sensitive gene | No specific phenotype assigned in the review | Unclear | Highlighted in a later autoimmune case report, not as a core dosage-sensitive 18p review gene (pqac-00000009) |
| USP14 | Not specified in the review pages provided | Deubiquitinating enzyme involved in proteostasis | Not classified in Hasi-Zogaj 2015 as a key dosage-sensitive gene | No specific phenotype assigned in the review | Unclear | Cited in later case literature as a potentially relevant deleted immune-modifying gene, but not part of the core 2015 dosage map summarized here (pqac-00000009) |


*Table: This table summarizes the principal chromosome 18p genes discussed as dosage-sensitive, conditionally dosage-sensitive, or candidate risk genes in the Hasi-Zogaj 2015 review, with later context for several immune-related genes. It is useful for linking deletion breakpoints to expected phenotypes and for distinguishing established haploinsufficiency from low-penetrance or modifier effects.*