C1ORF185

Chr 1

chromosome 1 open reading frame 185

NCBI Gene: 284546 ENSG00000204006 UniProt: Q5T7R7 OMIM: 621135

The protein encoded by this gene is predicted to be a membrane-associated protein, though its specific function remains unclear. Mutations cause autosomal recessive disorders including developmental and epileptic encephalopathy, microcephaly, and severe intellectual disability with onset in infancy or early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.81

Clinical Summary— C1ORF185

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 VUS of 4 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.38

OE 1.14 (0.68–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.09Z-score

OE missense 0.66 (0.53–0.83)

53 obs / 80.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.14 (0.68–1.81)

0≤0.351.4

Missense OE?0.66 (0.53–0.83)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 9 / 7.9Missense obs/exp: 53 / 80.4Syn Z: 0.76

ClinVar Variant Classifications

4 submitted variants in ClinVar

ClinVar

Classification Summary

VUS3

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	3	3
Likely Benign	0	0
Benign	0	0
Total	3	3

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

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7 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap C1ORF185 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →