ROPN1

Chr 3

rhophilin associated tail protein 1

Also known as: CT91, ODF6, RHPNAP1, ROPN1A, ropporin

NCBI Gene: 54763 ENSG00000065371 UniProt: Q9HAT0 OMIM: 611757

The protein is a component of the sperm fibrous sheath that interacts with signaling proteins including rhophilin and A-kinase anchoring proteins to regulate sperm motility and capacitation. Loss-of-function mutations cause male infertility due to defective sperm function. The gene shows low constraint against loss-of-function variants, and inheritance would be autosomal recessive for male infertility phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is found in the fibrous sheath of spermatazoa, where it interacts with rhophilin, a Rho GTPase binding protein. The encoded protein also can bind an A-kinase anchoring protein (AKAP110) and a calcium-binding tyrosine phosphorylation-regulated protein (CABYR). This protein may be involved in sperm motility and has been shown to be a cancer-testis antigen in hematologic malignancies. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.42

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.67

OE 0.76 (0.43–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.84–1.15)

116 obs / 118.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.43–1.42)

0≤0.351.4

Missense OE?0.98 (0.84–1.15)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 7 / 9.2Missense obs/exp: 116 / 118.2Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in ROPN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

222 rare PASS variants

Rare truncating (LoF)

1 in 2,500

35 rare PASS variants

Rare synonymous (reference)

1 in 270

93 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ROPN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 400	1 in 3,300
South Asian	~43k	1 in 180	1 in 1,500
Remaining (unassigned)	~30k	1 in 160	1 in 3,800
European (Finnish)	~27k	1 in 430	≈ 1 in 13,000
Admixed American	~22k	1 in 130	1 in 1,100
African / African American	~21k	1 in 140	1 in 2,800
East Asian	~20k	1 in 280	1 in 2,800
Ashkenazi Jewish	~13k	1 in 520	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 180	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 4 poorly covered. Genomes: 4 of 5 (exon 4 below).? see exons ↓