RCSD1

Chr 1

RCSD domain containing 1

Also known as: CAPZIP, MK2S4

NCBI Gene: 92241 ENSG00000198771 UniProt: Q6JBY9 OMIM: 610579

The RCSD1 protein binds actin filaments and is predicted to function in the WASH complex at early endosomes, with stress-induced phosphorylation potentially regulating actin filament remodeling. Mutations in RCSD1 cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.62).

OMIM ResearchSummary from RefSeq, UniProt

Enables actin filament binding activity. Involved in cellular hyperosmotic response. Predicted to be located in actin filament. Predicted to be part of WASH complex. Predicted to be active in early endosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.62

Clinical Summary— RCSD1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

71 VUS of 82 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.036

Z-score 2.80

OE 0.31 (0.17–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.44Z-score

OE missense 1.08 (0.97–1.20)

249 obs / 230.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.31 (0.17–0.62)

0≤0.351.4

Missense OE?1.08 (0.97–1.20)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 19.2Missense obs/exp: 249 / 230.1Syn Z: 0.19

This gene — mechanism propensity

0.6161th %ile

GOF

0.6149th %ile

LOF

0.4037th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS71

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	71	71
Likely Benign	4	4
Benign	0	0
Total	75	75

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap RCSD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →