GIMAP5

Chr 7AR

GTPase, IMAP family member 5

Also known as: HIMAP3, IAN-5, IAN4, IAN4L1, IAN5, IMAP3, IROD, NCPH2

NCBI Gene: 55340ENSG00000196329UniProt: Q96F15

This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. In humans, the IAN subfamily genes are located in a cluster at 7q36.1. This gene encodes an antiapoptotic protein that functions in T-cell survival. Polymorphisms in this gene are associated with systemic lupus erythematosus. Read-through transcription exists between this gene and the neighboring upstream GIMAP1 (GTPase, IMAP family member 1) gene. [provided by RefSeq, Dec 2010]

Primary Disease Associations & Inheritance

Portal hypertension, noncirrhotic, 2MIM #619463
AR
103
ClinVar variants
71
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— GIMAP5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 22 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.88LOEUF
pLI 0.097
Z-score 0.09
OE 0.90 (0.25–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.55Z-score
OE missense 1.12 (0.99–1.27)
183 obs / 163.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.90 (0.25–1.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (0.99–1.27)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 1 / 1.1Missense obs/exp: 183 / 163.2Syn Z: -1.19

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic6
VUS22
Likely Benign8
Benign1
Conflicting1
65
Pathogenic
6
Likely Pathogenic
22
VUS
8
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
65
0
65
Likely Pathogenic
0
3
3
0
6
VUS
0
12
10
0
22
Likely Benign
0
6
0
2
8
Benign
0
0
0
1
1
Conflicting
—1
Total021783103

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

View in ClinVar →

Protein Context — Lollipop Plot

GIMAP5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Portal hypertension, noncirrhotic, 2

MIM #619463

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Both Gimap5 and the diabetogenic BBDP allele of Gimap5 induce apoptosis in T cells.
Dalberg U et al.·Int Immunol
2007
Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.
Sadler MC et al.·Nat Commun
2025
Loss of GTPase of immunity-associated protein 5 (Gimap5) promotes pathogenic CD4(+) T-cell development and allergic airway disease.
Patterson AR et al.·J Allergy Clin Immunol
2019
Combined single-cell RNA-seq and bulk RNA-seq construction of M2 TAMs signature for predicting HNSCC prognosis and immunotherapy.
Wang J et al.·Front Immunol
2025
A novel iTreg-related signature for prognostic prediction in lung adenocarcinoma.
Zhang J et al.·Cancer Sci
2024
A Nomogram Combining Two Novel Biomarkers for Predicting Lung Adenocarcinoma in Ground-Glass Nodule Patients.
Li Y et al.·Hum Mutat
2025Cohort
IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.
Shin JH et al.·Genes Immun
2007Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools