UBFD1

Chr 16

ubiquitin family domain containing 1

Also known as: UBPH

NCBI Gene: 56061 ENSG00000103353 UniProt: O14562 OMIM: 621059

UBFD1 encodes a protein that binds RNA and cadherins and may regulate NF-kappa-B signaling. Mutations cause neurodevelopmental disorders with intellectual disability, and the gene shows autosomal recessive inheritance. This gene is highly constrained against loss-of-function variation (pLI 0.94, LOEUF 0.35), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity and cadherin binding activity. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.35

Clinical Summary— UBFD1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 51 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.942

Z-score 3.14

OE 0.07 (0.03–0.35)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.04Z-score

OE missense 0.77 (0.66–0.89)

122 obs / 158.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.35)

0≤0.351.4

Missense OE?0.77 (0.66–0.89)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 1 / 13.4Missense obs/exp: 122 / 158.8Syn Z: 0.93

This gene — mechanism propensity

0.2798th %ile

GOF

0.2895th %ile

LOF

0.73top 10%

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

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS51

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	2	2
Likely Pathogenic	0	0	0
VUS	50	1	51
Likely Benign	0	0	0
Benign	0	0	0
Total	50	3	53

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap UBFD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →