TTC21A

protein-coding

tetratricopeptide repeat domain 21A, the group of MicroRNA protein coding host genes|IFT-A complex|Tetratricopeptide repeat domain containing

Gene summary

Involved in flagellated sperm motility and spermatid development. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle A. Implicated in spermatogenic failure 37. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001366900.1

Inheritance

ClinVar variants

P:10U:208B:39

Top phenotype

Spermatogenic failure 37

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr3:39,107,680-39,138,903

External References & Databases

Ensembl (ENSG00000168026)

Transcript & Mutation Effects

hg38 • Region Span ~31.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 37STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032744

Submitter: Labcorp Genetics (formerly Invitae)

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 37AR

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: 30929735

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTC21A variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 212

not providedTotal: 21

TTC21A-related disorderTotal: 21

Spermatogenic failure 37Total: 11

Abnormal sperm morphologyTotal: 1

Reduced sperm motilityTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001366900.1. 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	14 clinvar	4 clinvar	20
missense	1 clinvar		201 clinvar	11 clinvar	10 clinvar	223
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar	4 clinvar			10
Total	5	5	208	25	14	257

Highest pathogenic variant AF is 0.000927

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001366900.1	RefSeq	NP_001353829.1	29	MANE Select
ENST00000683103.1	Ensembl	ENSP00000507739.1	29	MANE Select
NM_001105513.3	RefSeq	NP_001098983.2	28	Standard
NM_001366899.1	RefSeq	NP_001353828.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intraciliary retrograde transport
protein localization to cilium

Cellular Component

cilium
intraciliary transport particle A

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000431162
Coding exons: 29
Length: 31243
Individuals with no LoFs: 124547
Homozygous LoFs: 0
Heterozygous LoFs: 263
Defined: 124810
p: 0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.949	647	719	0.900	0.0000386	8690
Missense (PolyPhen)		173	202.53	0.85418		2497
Synonymous	0.164	289	293	0.988	0.0000167	2470
Loss of Function	2.35	48	69.1	0.694	0.00000330	869

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00093	0.00093	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00067	0.00067	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.00049	0.00049	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0985

Intolerance Scores

LoFtool: 0.903
RVIS EVS: 0.68
RVIS percentile EVS: 84.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.405

Gene Damage Prediction

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