TEX14

protein-coding

testis expressed 14, intercellular bridge forming factor, the group of Ankyrin repeat domain containing

Gene summary

The protein encoded by this gene is necessary for intercellular bridges in germ cells, which are required for spermatogenesis. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

MANE transcript

NM_031272.5

Inheritance

AD, AR

ClinVar variants

P:14U:223B:45

Top phenotype

Spermatogenic failure 23

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr17:58,556,678-58,692,055

External References & Databases

Ensembl (ENSG00000121101)

Transcript & Mutation Effects

hg38 • Region Span ~135.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 23AR

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: 28206990

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TEX14 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 233

not providedTotal: 24

Spermatogenic failure 23Total: 13

TEX14-related disorderTotal: 12

Non-obstructive azoospermiaTotal: 11

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031272.5. 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			2 clinvar	9 clinvar	4 clinvar	15
missense	1 clinvar	1 clinvar	216 clinvar	29 clinvar	2 clinvar	249
nonsense	3 clinvar	3 clinvar	3 clinvar			9
start loss						0
frameshift	3 clinvar	2 clinvar				5
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar	1 clinvar		4
Total	7	7	223	39	6	282

Highest pathogenic variant AF is 0.00028747917

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031272.5	RefSeq	NP_112562.3	31	MANE Select
ENST00000349033.10	Ensembl	ENSP00000268910.8	31	MANE Select
NM_001201457.2	RefSeq	NP_001188386.1	32	Standard
NM_198393.4	RefSeq	NP_938207.2	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
mitotic spindle assembly checkpoint
male meiotic nuclear division
attachment of spindle microtubules to kinetochore
negative regulation of protein binding

Molecular Function

protein kinase activity
protein binding
ATP binding
protein kinase binding

Cellular Component

kinetochore
condensed chromosome kinetochore
cell
cytoplasm
midbody

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000240361
Coding exons: 32
Length: 135378
Individuals with no LoFs: 125410
Homozygous LoFs: 0
Heterozygous LoFs: 337
Defined: 125747
p: 0.00134

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.406	831	799	1.04	0.0000417	9842
Missense (PolyPhen)		252	219.43	1.1484		2696
Synonymous	0.484	293	304	0.965	0.0000175	2817
Loss of Function	1.90	65	83.8	0.776	0.00000434	989

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0.0024	0.0025	notable
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.00093	0.00091	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro (By similarity). {ECO:0000250}.;
Disease: DISEASE: Spermatogenic failure 23 (SPGF23) [MIM:617707]: An infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia. {ECO:0000269|PubMed:28206990}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.360
RVIS EVS: -0.87
RVIS percentile EVS: 10.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.302

Gene Damage Prediction

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