UFC1

Chr 1AR

ubiquitin-fold modifier conjugating enzyme 1

Also known as: HSPC155, NEDSG

NCBI Gene: 51506 ENSG00000143222 UniProt: Q9Y3C8 OMIM: 610554

UFC1 encodes an E2-like enzyme that catalyzes the conjugation of ubiquitin-fold modifier-1 (UFM1) to target proteins, a process involved in ribosome recycling, DNA damage response, and reticulophagy. Autosomal recessive mutations cause a neurodevelopmental disorder with spasticity and poor growth. The gene shows tolerance to loss-of-function variants (pLI 0.004, LOEUF 0.91), consistent with the recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

UFC1 is an E2-like conjugating enzyme for ubiquitin-fold modifier-1 (UFM1; MIM 610553) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Mar 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with spasticity and poor growthMIM #618076

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with spasticity and poor growth; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

—

Mechanism

📖

GeneReview available — UFC1

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?

0.91LOEUF

pLI 0.004

Z-score 1.82

OE 0.46 (0.25–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.23Z-score

OE missense 0.93 (0.79–1.11)

89 obs / 95.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.25–0.91)

0≤0.351.4

Missense OE?0.93 (0.79–1.11)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 6 / 13.1Missense obs/exp: 89 / 95.4Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in UFC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

200 rare PASS variants

Rare truncating (LoF)

1 in 4,700

36 rare PASS variants

Rare synonymous (reference)

1 in 430

68 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UFC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 440	1 in 4,100
South Asian	~43k	1 in 230	1 in 2,100
Remaining (unassigned)	~30k	1 in 400	1 in 3,400
European (Finnish)	~27k	1 in 2,100	none seen
Admixed American	~22k	1 in 410	≈ 1 in 22,000
African / African American	~21k	1 in 590	≈ 1 in 4,200
East Asian	~20k	1 in 570	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 2,600	none seen
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓