C14orf39

protein-coding

chromosome 14 open reading frame 39

Gene summary

Involved in homologous chromosome pairing at meiosis. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_174978.3

Inheritance

ClinVar variants

P:8U:11B:8

Top phenotype

Spermatogenic failure 52; Premature ovarian failure 18

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr14:60,396,469-60,515,543

External References & Databases

Ensembl (ENSG00000179008)

Transcript & Mutation Effects

hg38 • Region Span ~119.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 18LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030939

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 52LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030938

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 52; Premature ovarian failure 18AR

Manifestation: Genitourinary; Obstetric

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: 33508233

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C14orf39 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 8

Spermatogenic failure 52Total: 8

not specifiedTotal: 8

Premature ovarian failure 18Total: 6

Non-obstructive azoospermiaTotal: 3

C14orf39-related disorderTotal: 2

Inherited primary ovarian failureTotal: 1

AzoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_174978.3. 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			1 clinvar	3 clinvar		4
missense			9 clinvar	4 clinvar	1 clinvar	14
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift	4 clinvar	2 clinvar				6
splice donor/acceptor (+/-2bp)						0
Total	6	2	11	7	1	27

Highest pathogenic variant AF is 0.00004123635

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_174978.3	RefSeq	NP_777638.3	17	MANE Select
ENST00000321731.8	Ensembl	ENSP00000324920.3	17	MANE Select
ENST00000498565.5	Ensembl	ENSP00000451937.1	4	Standard
ENST00000555476.5	Ensembl	ENSP00000451665.1	4	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321731
Coding exons: 17
Length: 119075
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125696
p: 0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.218	273	263	1.04	0.0000122	3879
Missense (PolyPhen)		48	47.089	1.0193		661
Synonymous	-1.18	102	88.0	1.16	0.00000440	967
Loss of Function	2.95	15	33.4	0.449	0.00000155	493

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000055	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination. Required for the appropriate processing of intermediate recombination nodules before crossover formation. {ECO:0000250|UniProtKB:Q9CTN5}.;

Intolerance Scores

RVIS EVS: 1.18
RVIS percentile EVS: 92.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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