USP1

Chr 1

ubiquitin specific peptidase 1

Also known as: UBP

NCBI Gene: 7398 ENSG00000162607 OMIM: 603478

This protein is a deubiquitinating enzyme that removes ubiquitin from key DNA repair proteins, specifically regulating the Fanconi anemia pathway and DNA translesion synthesis through deubiquitination of FANCD2 and PCNA. Biallelic mutations cause Fanconi anemia with short stature, microcephaly, and developmental delay, following an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function variants, reflecting its critical role in DNA repair mechanisms.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. The protein specifically deubiquitinates a protein in the Fanconi anemia (FA) DNA repair pathway. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanism

Clinical Summary— USP1

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ClinVar Variants

81 VUS of 94 total submissions

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Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.3793th %ile

GOF

0.2795th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

VUS81

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	81	0	81
Likely Benign	3	0	3
Benign	0	2	2
Total	84	2	86

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap USP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →