TTC21B

Chr 2ADAR

tetratricopeptide repeat domain 21B

Also known as: ATD4, CFAP60, FAP60, FLA17, IFT139, IFT139B, JBTS11, NPHP12

NCBI Gene: 79809ENSG00000123607UniProt: Q7Z4L5

This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [provided by RefSeq, Oct 2011]

Primary Disease Associations & Inheritance

Nephronophthisis 12MIM #613820
ADAR
Short-rib thoracic dysplasia 4 with or without polydactylyMIM #613819
AR
UniProtJoubert syndrome 11
177
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TTC21B
🧬
Gene-Disease Validity (ClinGen)
nephronophthisis 12 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 88 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.85LOEUF
pLI 0.000
Z-score 2.64
OE 0.68 (0.54–0.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.41Z-score
OE missense 1.04 (0.98–1.11)
724 obs / 693.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.54–0.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.98–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 53 / 78.2Missense obs/exp: 724 / 693.7Syn Z: -0.92

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic10
VUS88
Likely Benign65
Conflicting1
13
Pathogenic
10
Likely Pathogenic
88
VUS
65
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
8
0
13
Likely Pathogenic
6
0
4
0
10
VUS
1
81
4
2
88
Likely Benign
0
1
27
37
65
Benign
0
0
0
0
0
Conflicting
—1
Total12824339177

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

View in ClinVar →

Protein Context — Lollipop Plot

TTC21B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Nephronophthisis 12

MIM #613820

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Short-rib thoracic dysplasia 4 with or without polydactyly

MIM #613819

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TTC21B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.
Qin Y et al.·BMC Med Genomics
2023Cohort
Clinical report and genetic analysis of rare premature infant nephronophthisis caused by biallelic TTC21B variants.
Li Y et al.·Mol Genet Genomic Med
2024Review
Lethal neonatal respiratory failure due to biallelic variants in BBS1 and monoallelic variant in TTC21B.
Viehl L et al.·Pediatr Nephrol
2023
A single heterozygous nonsense mutation in the TTC21B gene causes adult-onset nephronophthisis 12: A case report and review of literature.
Wang D et al.·Mol Genet Genomic Med
2022Review
Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.
Chen W et al.·Hum Genomics
2022Cohort
[Clinical phenotype analysis of 6 cases of TTC21B gene related nephronophthisis].
Zhang J et al.·Zhonghua Er Ke Za Zhi
2022Cohort
Kidney failure in Bardet-Biedl syndrome.
Meyer JR et al.·Clin Genet
2022
Syndromic ciliopathy: a taiwanese single-center study.
Pan YW et al.·BMC Med Genomics
2024
Contribution of the TTC21B gene to glomerular and cystic kidney diseases.
Bullich G et al.·Nephrol Dial Transplant
2017
[Clinical features and TTC21B genotype of a child with nephronophthisis type 12].
Jian S et al.·Zhongguo Dang Dai Er Ke Za Zhi
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools