RUSF1

Chr 16

RUS family member 1

Also known as: C16orf58, RUS

NCBI Gene: 64755 ENSG00000140688 UniProt: Q96GQ5

RUSF1 encodes a transmembrane protein with a conserved DUF647 domain that may mediate protein-protein interactions. Mutations cause autosomal recessive intellectual disability with microcephaly, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, consistent with its role in neurodevelopmental disorders.

ResearchSummary from RefSeq

This gene encodes a putative transmembrane protein containing a conserved DUF647 domain that may be involved in protein-protein interaction. The encoded protein is related to a plant protein that participates in ultraviolet B light-sensing during root morphogenesis. [provided by RefSeq, Feb 2013]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.39

Clinical Summary— RUSF1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 48 VUS of 100 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?

1.39LOEUF

pLI 0.000

Z-score -0.01

OE 1.00 (0.73–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.03 (0.93–1.14)

269 obs / 261.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.00 (0.73–1.39)

0≤0.351.4

Missense OE?1.03 (0.93–1.14)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 26 / 26.0Missense obs/exp: 269 / 261.0Syn Z: 0.57

This gene — mechanism propensity

0.6939th %ile

GOF

0.5367th %ile

LOF

0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic4

VUS48

Likely Benign6

Benign2

Conflicting6

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	4	0	0	0	4
VUS	1	36	4	7	48
Likely Benign	0	2	3	1	6
Benign	0	1	1	0	2
Conflicting	—				6
Total	5	39	8	8	66

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap RUSF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →