UFM1

Chr 13AR

ubiquitin fold modifier 1

Also known as: BM-002, C13orf20, HLD14

NCBI Gene: 51569ENSG00000120686UniProt: P61960

UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1; MIM 610552) and E2-like conjugating enzyme UFC1 (MIM 610554) in a manner analogous to ubiquitylation (see UBE2M; MIM 603173) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Dec 2008]

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 14MIM #617899
AR
0
Active trials
53
Pathogenic / LP
101
ClinVar variants
43
Pubs (1 yr)
0.6
Missense Z
1.03
LOEUF
Clinical Summary— UFM1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 24 VUS of 101 total submissions
📖
GeneReview available — UFM1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.157
Z-score 1.53
OE 0.33 (0.13–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.62Z-score
OE missense 0.74 (0.56–0.99)
33 obs / 44.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.13–1.03)
0≤0.351.4
Missense OE0.74 (0.56–0.99)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 2 / 6.1Missense obs/exp: 33 / 44.6Syn Z: 0.49
DN
DN
0.75top 25%
GOF
0.5169th %ile
LOF
0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic4
VUS24
Likely Benign20
Benign4
49
Pathogenic
4
Likely Pathogenic
24
VUS
20
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
1
2
1
0
4
VUS
2
18
4
0
24
Likely Benign
0
2
9
9
20
Benign
0
0
3
1
4
Total3226610101

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

View in ClinVar →

UFM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

UFM1-related severe early-onset encephalopathy with progressive microcephaly

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients