TECPR2

Chr 14AR

tectonin beta-propeller repeat containing 2

Also known as: HSAN9, KIAA0329, SPG49

NCBI Gene: 9895ENSG00000196663UniProt: O15040

The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Neuropathy, hereditary sensory and autonomic, type IX, with developmental delayMIM #615031
AR
682
ClinVar variants
63
Pathogenic / LP
0.58
pLI score
0
Active trials
Clinical Summary— TECPR2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
63 Pathogenic / Likely Pathogenic· 203 VUS of 682 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.35LOEUF
pLI 0.580
Z-score 5.60
OE 0.22 (0.14–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
1.74Z-score
OE missense 0.83 (0.78–0.88)
689 obs / 829.9 exp
Tolerant

Mild missense constraint

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.0.22 (0.14–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.78–0.88)
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.1.00
0≤1.21.6
LoF obs/exp: 13 / 59.7Missense obs/exp: 689 / 829.9Syn Z: 0.02

ClinVar Variant Classifications

682 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic27
VUS203
Likely Benign412
Benign2
Conflicting2
36
Pathogenic
27
Likely Pathogenic
203
VUS
412
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
20
1
36
Likely Pathogenic
19
0
8
0
27
VUS
0
172
22
9
203
Likely Benign
0
7
150
255
412
Benign
0
0
2
0
2
Conflicting
—2
Total33180202265682

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

View in ClinVar →

Protein Context — Lollipop Plot

TECPR2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TECPR2-related hereditary spastic paraparesis

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay

MIM #615031

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TECPR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.
Neuser S et al.·Hum Mutat
2021
Blended phenotype of TECPR2-associated hereditary sensory-autonomic neuropathy and Temple syndrome.
Zubair U et al.·Ann Clin Transl Neurol
2025Case report
Novel TECPR2 variant in two cases of hereditary sensory and autonomic neuropathy type 9: insights from genetic characterization and comprehensive literature review.
Moeinafshar A et al.·BMC Neurol
2024Review
TECPR2-related hereditary sensory and autonomic neuropathy in two siblings from Palestine.
Khalaf-Nazzal R et al.·Am J Med Genet A
2024Case report
A novel SNP of TECPR2 gene associated with heat tolerance in Chinese cattle.
Ma X et al.·Anim Biotechnol
2023
TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.
Hahn K et al.·PLoS One
2015
Neuropathology-driven Whole-genome Sequencing Study Points to Novel Candidate Genes for Healthy Brain Aging.
Alexander J et al.·Alzheimer Dis Assoc Disord
2019
Investigating the Causal Effects of Exercise-Induced Genes on Sarcopenia.
Wang L et al.·Int J Mol Sci
2024
Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report.
Guan Y et al.·BMC Neurol
2022Case 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