GEMIN5

Chr 5AR

gem nuclear organelle associated protein 5

Also known as: GEMIN-5, NEDCAM

NCBI Gene: 25929ENSG00000082516UniProt: Q8TEQ6

This gene encodes a WD repeat protein that is a component of the survival of motor neurons (SMN) complex. The SMN complex plays a critical role in mRNA splicing through the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), and may also mediate the assembly and transport of other classes of ribonucleoproteins. The encoded protein is the snRNA-binding component of the SMN complex. Dysregulation of this gene may play a role in alternative mRNA splicing and tumor cell motility. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with cerebellar atrophy and motor dysfunctionMIM #619333
AR
383
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GEMIN5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 265 VUS of 383 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.
0.75LOEUF
pLI 0.000
Z-score 3.43
OE 0.59 (0.46–0.75)
Tolerant

Typical tolerance to LoF variation

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.
0.07Z-score
OE missense 0.99 (0.94–1.05)
781 obs / 786.3 exp
Tolerant

Mild missense constraint

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.0.59 (0.46–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.94–1.05)
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.1.06
0≤1.21.6
LoF obs/exp: 47 / 80.1Missense obs/exp: 781 / 786.3Syn Z: -0.77

ClinVar Variant Classifications

383 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic19
VUS265
Likely Benign30
Benign4
Conflicting5
24
Pathogenic
19
Likely Pathogenic
265
VUS
30
Likely Benign
4
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
5
15
0
24
Likely Pathogenic
8
4
7
0
19
VUS
2
252
11
0
265
Likely Benign
0
18
1
11
30
Benign
0
4
0
0
4
Conflicting
—5
Total142833411347

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

View in ClinVar →

Protein Context — Lollipop Plot

GEMIN5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GEMIN5-related neurodevelopmental disorder with cerebellar atrophy and motor dysfunction

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction

MIM #619333

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.
Kour S et al.·Nat Commun
2021
N 6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer.
Su J et al.·Cancer Res
2023
Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies.
Zhang J et al.·Brain Behav
2024Case report
A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy.
Ibrahim N et al.·Genes (Basel)
2023
Functional and structural deficiencies of Gemin5 variants associated with neurological disorders.
Francisco-Velilla R et al.·Life Sci Alliance
2022Functional
Pathogenic variants in the survival of motor neurons complex gene GEMIN5 cause cerebellar atrophy.
Saida K et al.·Clin Genet
2021
RNA m7G methylation regulators and targets significantly contribute to chronic obstructive pulmonary disease.
Zhu C et al.·Sci Rep
2025
CAPRIN1(P512L) causes aberrant protein aggregation and associates with early-onset ataxia.
Delle Vedove A et al.·Cell Mol Life Sci
2022Case report
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