FSIP2

Chr 2AR

fibrous sheath interacting protein 2

Also known as: SPGF34

NCBI Gene: 401024ENSG00000188738UniProt: Q5CZC0OMIM: 615796

The protein is a structural component of the sperm fibrous sheath that is specifically expressed in spermatogenic cells during the postmeiotic phase of spermatogenesis. Mutations cause spermatogenic failure 34, an autosomal recessive condition leading to male infertility. This gene is highly constrained against loss-of-function variants, indicating its critical role in normal sperm development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.511 OMIM phenotype
Clinical Summary— FSIP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
181 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.51LOEUF
pLI 0.000
Z-score 7.35
OE 0.43 (0.35–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.31Z-score
OE missense 0.83 (0.80–0.86)
2489 obs / 2998.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.43 (0.35–0.51)
0≤0.351.4
Missense OE0.83 (0.80–0.86)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 81 / 190.4Missense obs/exp: 2489 / 2998.7Syn Z: 3.77
DN
0.5869th %ile
GOF
0.94top 5%
LOF
0.2484th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

200 submitted variants in ClinVar

ClinVar

Classification Summary

VUS181
Likely Benign19
181
VUS
19
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
175
6
0
181
Likely Benign
0
18
1
0
19
Benign
0
0
0
0
0
Total019370200

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

View in ClinVar →

Protein Context — Lollipop Plot

FSIP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Novel mutations in FSIP2 cause male infertility through multiple morphological abnormalities of the sperm flagella.
Hussain M et al.·Asian J Androl
2026Open Access
[Clinical and genetic analysis of a patient with FSIP2 compound heterozygous variants causing multiple morphological abnormalities of sperm flagella].
Chen YQ et al.·Zhonghua Nan Ke Xue
2025
Novel variants of FSIP2 and SPEF2 cause varying degrees of spermatozoa damage in MMAF patients and favorable ART outcomes.
Dai CL et al.·J Assist Reprod Genet
2025Cohort
Novel FSIP2 Variants Induce Super-Length Mitochondrial Sheath and Asthenoteratozoospermia in Humans.
Lv M et al.·Int J Biol Sci
2023Open Access
Novel Compound Heterozygous Mutation in FSIP2 Causes Multiple Morphological Abnormalities of the Sperm Flagella (MMAF) and Male Infertility.
Hou M et al.·Reprod Sci
2022
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients