TECPR2

protein-coding

tectonin beta-propeller repeat containing 2

Gene summary

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]

Previous symbols:

KIAA0329

MANE transcript

NM_014844.5

Inheritance

ClinVar variants

P:134U:376B:696

Top phenotype

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

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr14:102,362,941-102,502,477

External References & Databases

Ensembl (ENSG00000196663)

Transcript & Mutation Effects

hg38 • Region Span ~139.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegia 49SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014016

Submitter: Orphanet

hereditary spastic paraplegia 49DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014016

Submitter: Natera

hereditary spastic paraplegia 49STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014016

Submitter: Labcorp Genetics (formerly Invitae)

hereditary spastic paraplegia 49STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014016

Submitter: G2P

hereditary spastic paraplegia 49STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014016

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

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

Manifestation: Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23176824; 26542466; 27406698; 32209221

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TECPR2 variants in ClinVar

13 Conditions Cataloged

Hereditary spastic paraplegia 49Total: 1323

not providedTotal: 164

Inborn genetic diseasesTotal: 136

not specifiedTotal: 75

Hereditary spastic paraplegiaTotal: 65

TECPR2-related disorderTotal: 40

Intellectual disabilityTotal: 2

Sensory autonomic neuropathy with intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014844.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		13 clinvar	665 clinvar	3 clinvar	682
missense	1 clinvar		358 clinvar	24 clinvar	4 clinvar	387
nonsense	21 clinvar	16 clinvar	1 clinvar			38
start loss						0
frameshift	38 clinvar	37 clinvar	1 clinvar			76
splice donor/acceptor (+/-2bp)		20 clinvar	3 clinvar			23
Total	61	73	376	689	7	1206

Highest pathogenic variant AF is 0.00007750419

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014844.5	RefSeq	NP_055659.2	19	MANE Select
ENST00000359520.12	Ensembl	ENSP00000352510.7	19	MANE Select
NM_001172631.3	RefSeq	NP_001166102.1	16	Standard
ENST00000558678.1	Ensembl	ENSP00000453671.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

autophagy

Molecular Function

protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359520
Coding exons: 19
Length: 139519
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.74	689	830	0.830	0.0000502	9189
Missense (PolyPhen)		139	220.61	0.63008		2431
Synonymous	0.0224	366	367	0.999	0.0000259	2821
Loss of Function	5.60	13	59.7	0.218	0.00000256	697

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.0032	0.0032	notable
East Asian	0.00055	0.00054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably plays a role as positive regulator of autophagy. {ECO:0000269|PubMed:23176824}.;

Intolerance Scores

LoFtool: 0.518
RVIS EVS: -0.47
RVIS percentile EVS: 22.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.658

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium