TTC21A

Chr 3AR

tetratricopeptide repeat domain 21A

Also known as: IFT139A, SPGF37, STI2, Thm2

This protein is required for intraflagellar transport and sperm flagellar formation during spermatogenesis. Mutations cause spermatogenic failure 37, characterized by male infertility due to defective sperm motility and development. The inheritance pattern is autosomal recessive.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryTTC21A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 197 VUS of 282 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.35
OE 0.69 (0.550.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.95Z-score
OE missense 0.90 (0.840.96)
647 obs / 718.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.550.88)
00.351.4
Missense OE0.90 (0.840.96)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 48 / 69.1Missense obs/exp: 647 / 718.6Syn Z: 0.16
DN
0.6649th %ile
GOF
0.6053th %ile
LOF
0.2775th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

282 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS197
Likely Benign22
Benign21
14
Pathogenic
4
Likely Pathogenic
197
VUS
22
Likely Benign
21
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
9
0
14
Likely Pathogenic
3
0
1
0
4
VUS
1
195
1
0
197
Likely Benign
0
11
1
10
22
Benign
0
15
0
6
21
Total82221216258

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TTC21A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →