UIMC1

Chr 5

ubiquitin interaction motif containing 1

Also known as: RAP80, X2HRIP110

NCBI Gene: 51720 ENSG00000087206 UniProt: Q96RL1 OMIM: 609433

The UIMC1 protein specifically recognizes and binds Lys-63-linked ubiquitinated histones at DNA damage sites, functioning as part of the BRCA1-A complex to recruit DNA repair machinery to double-strand breaks. Mutations cause autosomal recessive intellectual disability with microcephaly and variable features including growth retardation and facial dysmorphism. This gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected families.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a nuclear protein that interacts with Brca1 (breast cancer 1) in a complex to recognize and repair DNA lesions. This protein binds ubiquitinated lysine 63 of histone H2A and H2AX. This protein may also function as a repressor of transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— UIMC1

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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

1 unique Pathogenic / Likely Pathogenic· 83 VUS of 118 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?

0.65LOEUF

pLI 0.000

Z-score 3.27

OE 0.44 (0.30–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.90 (0.82–0.98)

340 obs / 379.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.30–0.65)

0≤0.351.4

Missense OE?0.90 (0.82–0.98)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 17 / 39.1Missense obs/exp: 340 / 379.2Syn Z: -0.24

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS83

Likely Benign6

Benign4

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	1	82	0	83
Likely Benign	0	6	0	6
Benign	0	1	3	4
Total	2	89	3	94

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

View in ClinVar →

57 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap UIMC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →