TECPR2

Chr 14AR

tectonin beta-propeller repeat containing 2

Also known as: HSAN9, KIAA0329, SPG49

NCBI Gene: 9895 ENSG00000196663 UniProt: O15040 OMIM: 615000

The TECPR2 protein functions as a positive regulator of autophagy, the cellular process that degrades damaged organelles and proteins. Autosomal recessive mutations cause hereditary sensory and autonomic neuropathy type IX with developmental delay, affecting both the peripheral nervous system and early neurodevelopment. The gene is highly constrained against loss-of-function variation (LOEUF 0.346), indicating that complete loss of protein function is likely not well tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.351 OMIM phenotype

Clinical Summary— TECPR2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.

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ClinVar Variants

140 unique Pathogenic / Likely Pathogenic· 398 VUS of 1595 total submissions

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GeneReview available — TECPR2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.74Z-score

OE missense 0.83 (0.78–0.88)

689 obs / 829.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.14–0.35)

0≤0.351.4

Missense OE?0.83 (0.78–0.88)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 13 / 59.7Missense obs/exp: 689 / 829.9Syn Z: 0.02

ClinVar Variant Classifications

1595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63

Likely Pathogenic77

VUS398

Likely Benign945

Benign67

Conflicting26

Pathogenic

Likely Pathogenic

398

VUS

945

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	53	1	8	1	63
Likely Pathogenic	70	0	7	0	77
VUS	0	355	32	11	398
Likely Benign	0	16	281	648	945
Benign	0	7	53	7	67
Conflicting	—				26
Total	123	379	381	667	1,576

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

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46 pathogenic / likely-pathogenic (of 63) ClinVar copy-number / structural variants overlap TECPR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →