C1ORF105

Chr 1

chromosome 1 open reading frame 105

NCBI Gene: 92346 ENSG00000180999 UniProt: O95561

The protein encoded by this gene has unknown function. Biallelic mutations cause a rare autosomal recessive disorder characterized by developmental delay, intellectual disability, and seizures. The gene shows low constraint against loss-of-function variants (pLI 0.00001, LOEUF 1.58), suggesting haploinsufficiency is likely tolerated.

Research

ResearchGenerating clinical summary…

LOEUF 1.58

Clinical Summary— C1ORF105

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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

7 unique Pathogenic / Likely Pathogenic· 61 VUS of 93 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?

1.58LOEUF

pLI 0.000

Z-score 0.29

OE 0.89 (0.52–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.90 (0.75–1.08)

84 obs / 93.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.89 (0.52–1.58)

0≤0.351.4

Missense OE?0.90 (0.75–1.08)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 8 / 9.0Missense obs/exp: 84 / 93.5Syn Z: 0.86

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS61

Likely Benign13

Benign5

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	1	2	0	0	3
VUS	2	58	1	0	61
Likely Benign	0	1	1	11	13
Benign	0	2	0	3	5
Conflicting	—				2
Total	5	65	2	14	88

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap C1ORF105 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →