RIN1

Chr 11

Ras and Rab interactor 1

NCBI Gene: 9610 ENSG00000174791 UniProt: Q13671

The protein functions as a Ras effector that modulates neuronal plasticity and memory formation by competing with RAF1 for Ras binding, enhancing ABL1/ABL2 signaling for cytoskeletal remodeling, and acting as a guanine nucleotide exchange factor for RAB5A to facilitate receptor endocytosis. Mutations in this gene cause autosomal recessive intellectual disability with macrocephaly, seizures, and distinctive facial features. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in intracellular signal transduction. Predicted to act upstream of or within associative learning; memory; and negative regulation of synaptic plasticity. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

GOF

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?

0.92LOEUF

pLI 0.000

Z-score 1.85

OE 0.59 (0.39–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.55Z-score

OE missense 0.93 (0.85–1.00)

410 obs / 442.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.39–0.92)

0≤0.351.4

Missense OE?0.93 (0.85–1.00)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 14 / 23.7Missense obs/exp: 410 / 442.7Syn Z: -1.26

Background carrier burden — how many people carry a rare variant somewhere in RIN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,114 rare PASS variants

Rare truncating (LoF)

1 in 740

185 rare PASS variants

Rare synonymous (reference)

1 in 88

486 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RIN1. 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 49	1 in 800
South Asian	~43k	1 in 41	1 in 980
Remaining (unassigned)	~30k	1 in 36	1 in 780
European (Finnish)	~27k	1 in 120	1 in 1,800
Admixed American	~22k	1 in 33	1 in 1,200
African / African American	~21k	1 in 27	1 in 570
East Asian	~20k	1 in 36	1 in 460
Ashkenazi Jewish	~13k	1 in 110	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 42	≈ 1 in 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): 9 of 10 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 10.? see exons ↓