SPSB4

Chr 3

splA/ryanodine receptor domain and SOCS box containing 4

Also known as: SSB-4, SSB4

NCBI Gene: 92369 ENSG00000175093 UniProt: Q96A44 OMIM: 611660

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including positive regulation of protein polyubiquitination; protein ubiquitination; and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.41LOEUF

pLI 0.000

Z-score 0.74

OE 0.72 (0.39–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.87Z-score

OE missense 0.81 (0.70–0.94)

135 obs / 166.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.39–1.41)

0≤0.351.4

Missense OE?0.81 (0.70–0.94)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 6 / 8.3Missense obs/exp: 135 / 166.6Syn Z: 0.54

Background carrier burden — how many people carry a rare variant somewhere in SPSB4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

432 rare PASS variants

Rare truncating (LoF)

1 in 4,800

56 rare PASS variants

Rare synonymous (reference)

1 in 330

215 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPSB4. 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 240	1 in 5,100
South Asian	~43k	1 in 150	1 in 3,400
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 7,300
European (Finnish)	~27k	1 in 710	1 in 2,500
Admixed American	~22k	1 in 110	≈ 1 in 18,000
African / African American	~21k	1 in 200	≈ 1 in 5,600
East Asian	~20k	1 in 130	≈ 1 in 4,600
Ashkenazi Jewish	~13k	1 in 430	≈ 1 in 3,800
Middle Eastern	~2,884	1 in 130	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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓