TSPEAR

Chr 21AR

thrombospondin type laminin G domain and EAR repeats

Also known as: C21orf29, DFNB98, ECTD14, STHAG10, TSP-EAR

TSPEAR encodes a protein containing a thrombospondin-type laminin G domain that regulates Notch signaling during tooth and hair follicle morphogenesis and may function in auditory system development. Mutations cause autosomal recessive deafness-98, ectodermal dysplasia with abnormalities of hair, teeth, and nails, and selective tooth agenesis. The gene follows autosomal recessive inheritance and primarily affects ectodermal-derived structures including the inner ear, teeth, hair, and nails.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 98MIM #614861
AR
Ectodermal dysplasia 14, hypohidrotic/hair/tooth/nail typeMIM #618180
AR
Tooth agenesis, selective, 10MIM #620173
AR
0
Active trials
12
Pubs (1 yr)
46
P/LP submissions
0%
P/LP missense
1.20
LOEUF
Mechanism
Clinical SummaryTSPEAR
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 243 VUS of 332 total submissions
📖
GeneReview available — TSPEAR
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.000
Z-score 0.67
OE 0.87 (0.651.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.95Z-score
OE missense 1.13 (1.051.22)
473 obs / 418.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.87 (0.651.20)
00.351.4
Missense OE1.13 (1.051.22)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 28 / 32.1Missense obs/exp: 473 / 418.2Syn Z: -0.54

ClinVar Variant Classifications

332 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic1
VUS243
Likely Benign38
Benign1
39
Pathogenic
1
Likely Pathogenic
243
VUS
38
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
35
0
39
Likely Pathogenic
1
0
0
0
1
VUS
1
238
4
0
243
Likely Benign
0
25
4
9
38
Benign
0
0
1
0
1
Total6263449322

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

View in ClinVar →

Protein Context — Lollipop Plot

TSPEAR · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →