PMFBP1

protein-coding

polyamine modulated factor 1 binding protein 1

Gene summary

Involved in spermatogenesis. Located in sperm head-tail coupling apparatus; sperm midpiece; and sperm principal piece. Implicated in spermatogenic failure 31. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_031293.3

Inheritance

ClinVar variants

P:14U:147B:24

Top phenotype

Spermatogenic failure 31

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr16:72,112,157-72,176,878

External References & Databases

Ensembl (ENSG00000118557)

Transcript & Mutation Effects

hg38 • Region Span ~64.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 31STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020852

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 31LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020852

Submitter: Ambry Genetics

spermatogenic failure 31STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020852

Submitter: PanelApp Australia

male infertility due to acephalic spermatozoaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0035153

Submitter: ClinGen

*PMFBP1* was first reported in relation to autosomal recessive male infertility due to acephalic spermatozoa in 2018 (*Zhu et al.*, PMID: 30032984). This condition is characterized by male infertility due to oligozoospermia with a high proportion (greater than 90%) of acephalic sperm. Nine variants (e.g. nonsense, frameshift, splice site mutation) that have been reported in eight probands in four publications (PMIDs: 30032984, 30298696, 35860846, 41462896) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is believed to be biallelic loss of function, as mutations of *PMFBP1* tend to cause failure in sperm head-tail coupling apparatus assembly (PMID:30032984). This gene-disease relationship is also supported by mouse models. (PMIDs:30032984, 30298696). *Pmfbp1 -/-* mouse models phenocopied acephalic spermatozoa syndrome in human patients, showing male infertility (PMID: 30032984, 30298696). In summary, there is definitive evidence supporting the relationship between *PMFBP1* and autosomal recessive male infertility due to acephalic spermatozoa. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Male Infertility GCEP on the meeting date April 1, 2026 (SOP Version 12).

Clinical Genomic Database (CGD)

Spermatogenic failure 31AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30032984

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PMFBP1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 156

Spermatogenic failure 31Total: 16

PMFBP1-related disorderTotal: 15

not providedTotal: 8

Abnormal sperm morphologyTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031293.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	2 clinvar	8
missense			144 clinvar	13 clinvar	3 clinvar	160
nonsense	4 clinvar	3 clinvar				7
start loss						0
frameshift	3 clinvar	3 clinvar				6
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	7	7	147	19	5	185

Highest pathogenic variant AF is 0.000095416064

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031293.3	RefSeq	NP_112583.2	20	MANE Select
ENST00000237353.15	Ensembl	ENSP00000237353.10	20	MANE Select
NM_001160213.2	RefSeq	NP_001153685.1	17	Standard
ENST00000355636.10	Ensembl	ENSP00000347854.6	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spermatogenesis
biological_process

Molecular Function

molecular_function

Cellular Component

cytoplasm
sperm connecting piece

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000237353
Coding exons: 20
Length: 64722
Individuals with no LoFs: 125283
Homozygous LoFs: 0
Heterozygous LoFs: 465
Defined: 125748
p: 0.00185

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.468	552	522	1.06	0.0000274	6710
Missense (PolyPhen)		136	131.53	1.034		1992
Synonymous	-1.19	234	212	1.10	0.0000120	1726
Loss of Function	0.857	55	62.3	0.883	0.00000320	729

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00098	0.00098	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0090	0.0091	notable
Finnish	0.0021	0.0021	notable
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0016	0.0015	notable
Other	0.0025	0.0024	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in sperm morphology especially the sperm tail and consequently affect fertility. May also be involved in the general organization of cellular cytoskeleton. {ECO:0000269|PubMed:1770140}.;

Intolerance Scores

LoFtool: 0.996
RVIS EVS: -0.66
RVIS percentile EVS: 16.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.188

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High