GPRIN1

Chr 5

G protein regulated inducer of neurite outgrowth 1

Also known as: GRIN1

NCBI Gene: 114787 ENSG00000169258 UniProt: Q7Z2K8 OMIM: 611239

GPRIN1 encodes a protein that binds phosphoproteins and is involved in neurite outgrowth and neuron projection development at the growth cone and plasma membrane. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function mutations (pLI 0.97, LOEUF 0.32), indicating that complete loss of protein function is typically not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable phosphoprotein binding activity. Predicted to be involved in neuron projection development. Predicted to be located in growth cone. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— GPRIN1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

154 VUS of 168 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.970

Z-score 3.69

OE 0.10 (0.04–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.34Z-score

OE missense 0.96 (0.89–1.03)

496 obs / 517.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.32)

0≤0.351.4

Missense OE?0.96 (0.89–1.03)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 19.7Missense obs/exp: 496 / 517.6Syn Z: 0.31

This gene — mechanism propensity

0.3892th %ile

GOF

0.3491th %ile

LOF

0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

VUS154

Likely Benign12

Benign2

154

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	154	0	154
Likely Benign	0	11	1	12
Benign	2	0	0	2
Total	2	165	1	168

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

View in ClinVar →

52 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap GPRIN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →