RWDD4

Chr 4

RWD domain containing 4

Also known as: FAM28A, RWDD4A

NCBI Gene: 201965 ENSG00000182552 UniProt: Q6NW29

The RWDD4 protein contains RWD and WD40 domains and functions in protein-protein interactions and cellular signaling pathways. Mutations cause autosomal recessive developmental delay with intellectual disability, seizures, and brain malformations including microcephaly and cerebellar hypoplasia. The gene shows tolerance to loss-of-function variants in the general population, consistent with the recessive inheritance pattern observed in affected individuals.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.017

Z-score 2.03

OE 0.39 (0.20–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.69Z-score

OE missense 0.80 (0.67–0.97)

79 obs / 98.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.82)

0≤0.351.4

Missense OE?0.80 (0.67–0.97)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 5 / 12.9Missense obs/exp: 79 / 98.3Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in RWDD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 480

186 rare PASS variants

Rare truncating (LoF)

1 in 3,700

38 rare PASS variants

Rare synonymous (reference)

1 in 710

57 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RWDD4. 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 470	1 in 3,100
South Asian	~43k	1 in 550	1 in 1,800
Remaining (unassigned)	~30k	1 in 650	≈ 1 in 10,000
European (Finnish)	~27k	1 in 550	none seen
Admixed American	~22k	1 in 290	≈ 1 in 10,000
African / African American	~21k	1 in 390	≈ 1 in 6,400
East Asian	~20k	1 in 640	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,883	1 in 270	≈ 1 in 2,800

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 8 coding exons well covered in gnomAD exomes; exon 7 poorly covered; exons 1, 5, 8 marginal. Genomes: all 8.? see exons ↓