C10ORF90

Chr 10

chromosome 10 open reading frame 90

Also known as: FATS, bA422P15.2

NCBI Gene: 118611 ENSG00000154493 UniProt: Q96M02 OMIM: 617735

The protein functions as a tumor suppressor that maintains the G2/M cell cycle checkpoint after DNA damage by activating p53 through ubiquitin ligase activity and preventing MDM2 binding. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay, typically presenting in infancy. This gene is extremely intolerant to loss-of-function variants, indicating it is under strong evolutionary constraint.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable histone deacetylase binding activity and ubiquitin protein ligase activity. Predicted to be involved in several processes, including protein stabilization; regulation of cell cycle process; and response to ionizing radiation. Located in cytoskeleton; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.21

Clinical Summary— C10ORF90

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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

8 VUS of 22 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?

1.21LOEUF

pLI 0.000

Z-score 0.69

OE 0.86 (0.62–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.45Z-score

OE missense 1.06 (0.98–1.15)

432 obs / 406.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.62–1.21)

0≤0.351.4

Missense OE?1.06 (0.98–1.15)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 24 / 28.0Missense obs/exp: 432 / 406.6Syn Z: 0.55

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

VUS8

Likely Benign1

Benign10

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	8	0	0	8
Likely Benign	0	1	0	0	1
Benign	1	3	1	5	10
Total	1	12	1	5	19

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap C10ORF90 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →