SUSD5

Chr 3

sushi domain containing 5

NCBI Gene: 26032 ENSG00000173705 UniProt: O60279 OMIM: 619917

The protein is predicted to bind hyaluronic acid and participate in Notch signaling pathways. Mutations cause autosomal recessive intellectual disability with seizures and spasticity. The gene shows minimal constraint against loss-of-function variants, which is consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq

Predicted to enable hyaluronic acid binding activity. Predicted to be involved in Notch signaling pathway. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score 0.37

OE 0.91 (0.62–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.90–1.07)

346 obs / 352.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.62–1.36)

0≤0.351.4

Missense OE?0.98 (0.90–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 17 / 18.7Missense obs/exp: 346 / 352.4Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in SUSD5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

831 rare PASS variants

Rare truncating (LoF)

1 in 1,400

130 rare PASS variants

Rare synonymous (reference)

1 in 93

337 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SUSD5. 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 89	1 in 1,700
South Asian	~43k	1 in 56	1 in 1,000
Remaining (unassigned)	~30k	1 in 47	1 in 540
European (Finnish)	~27k	1 in 120	1 in 3,800
Admixed American	~22k	1 in 58	1 in 750
African / African American	~21k	1 in 65	1 in 550
East Asian	~20k	1 in 65	1 in 610
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 65	≈ 1 in 2,900

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓