ROPN1B

Chr 3

rhophilin associated tail protein 1B

NCBI Gene: 152015 ENSG00000114547

ROPN1B encodes a protein that forms heterodimers with ROPN1L to maintain fibrous sheath integrity and enable sperm motility, participating in PKA-dependent signaling required for sperm capacitation. Mutations cause male infertility with asthenozoospermia (reduced sperm motility), inherited in an autosomal recessive pattern. This gene shows low constraint against loss-of-function variants, consistent with its specialized role in male fertility rather than essential cellular functions.

ResearchSummary from RefSeq, UniProt

Enables protein heterodimerization activity. Predicted to be involved in several processes, including flagellated sperm motility; protein localization to cilium; and sperm capacitation. Located in cytoplasm and motile cilium. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.46

Clinical Summary— ROPN1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

30 VUS of 36 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.46LOEUF

pLI 0.000

Z-score 0.55

OE 0.81 (0.48–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.48Z-score

OE missense 1.13 (0.97–1.30)

129 obs / 114.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.48–1.46)

0≤0.351.4

Missense OE?1.13 (0.97–1.30)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 8 / 9.8Missense obs/exp: 129 / 114.6Syn Z: 0.67

This gene — mechanism propensity

0.6261th %ile

GOF

0.73top 25%

LOF

0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction 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

36 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	30	30
Likely Benign	3	3
Benign	0	0
Total	33	33

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap ROPN1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →