TECPR2

tectonin beta-propeller repeat containing 2

Basic information

Region (hg38): 14:102362940-102502477

Previous symbols: [ "KIAA0329" ]

Links

ENSG00000196663 ∙ NCBI:9895 ∙ OMIM:615000 ∙ HGNC:19957 ∙ Uniprot:O15040 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 49 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 49 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 49 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay	AR	General	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	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	23176824; 26542466; 27406698; 32209221

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TECPR2 gene.

• Hereditary spastic paraplegia 49 (952 variants)
• not provided (170 variants)
• Hereditary spastic paraplegia (73 variants)
• Inborn genetic diseases (66 variants)
• not specified (33 variants)
• Sensory autonomic neuropathy with intellectual disability (1 variants)
• Inherited spastic paresis (1 variants)
• Intellectual disability, FRA12A type (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TECPR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	518	11	531
missense			221	9	7	237
nonsense	18	2				20
start loss						0
frameshift	28	15				43
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)		8				8
splice region			14	54	1	69
non coding				128	52	180
Total	46	25	227	656	70

Highest pathogenic variant AF is 0.0000723

Variants in TECPR2

This is a list of pathogenic ClinVar variants found in the TECPR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-102376439-A-G			Likely benign (Jun 14, 2018)
14-102376694-G-A		not specified	Likely benign (May 31, 2017)
14-102376702-A-C		not specified	Benign (Apr 15, 2016)
14-102376719-G-A		Hereditary spastic paraplegia 49	Likely benign (Sep 16, 2020)
14-102376720-C-T		not specified • Hereditary spastic paraplegia 49 • Hereditary spastic paraplegia	Benign (Dec 08, 2021)
14-102376729-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
14-102376730-G-A		Hereditary spastic paraplegia 49	Likely benign (Aug 20, 2023)
14-102376730-G-T		Hereditary spastic paraplegia 49	Likely benign (Feb 14, 2023)
14-102376736-A-G		Hereditary spastic paraplegia 49	Likely benign (Jul 02, 2022)
14-102376743-G-C		Hereditary spastic paraplegia	Uncertain significance (Dec 01, 2017)
14-102376745-T-C		Hereditary spastic paraplegia 49 • TECPR2-related disorder	Likely benign (Dec 09, 2023)
14-102376745-T-TA		Hereditary spastic paraplegia 49	Pathogenic (Nov 13, 2023)
14-102376748-A-G		Hereditary spastic paraplegia 49	Likely benign (Oct 27, 2021)
14-102376751-CAG-C		Hereditary spastic paraplegia 49	Pathogenic (Jan 28, 2023)
14-102376754-A-G		Hereditary spastic paraplegia 49	Likely benign (Dec 11, 2023)
14-102376755-G-T		Hereditary spastic paraplegia 49	Pathogenic (Mar 26, 2020)
14-102376760-C-T		Hereditary spastic paraplegia 49 • TECPR2-related disorder	Likely benign (Aug 16, 2023)
14-102376766-G-A		Hereditary spastic paraplegia 49	Likely benign (Jan 25, 2024)
14-102376766-G-C		Hereditary spastic paraplegia 49	Likely benign (Oct 06, 2023)
14-102376772-C-G		Hereditary spastic paraplegia 49	Pathogenic (Sep 18, 2023)
14-102376774-A-G		Hereditary spastic paraplegia 49 • Intellectual disability, FRA12A type • Inborn genetic diseases	Uncertain significance (Apr 19, 2022)
14-102376775-TCTC-T		Hereditary spastic paraplegia 49	Uncertain significance (Sep 02, 2021)
14-102376778-C-T		Hereditary spastic paraplegia 49	Likely benign (Sep 19, 2021)
14-102376788-A-G		Hereditary spastic paraplegia 49	Uncertain significance (Jun 04, 2022)
14-102376792-C-T			Uncertain significance (Apr 29, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TECPR2	protein_coding	protein_coding	ENST00000359520	19	139519

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.580	0.420	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.74	689	830	0.830	0.0000502	9189
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000339	0.000333
Ashkenazi Jewish	0.00322	0.00318
East Asian	0.000553	0.000544
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.000207	0.000202
Middle Eastern	0.000553	0.000544
South Asian	0.0000653	0.0000653
Other	0.000330	0.000326

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.238
• hipred: Y
• hipred_score: 0.563
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.658

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tecpr2

Gene ontology

• Biological process: autophagy
• Molecular function: protein binding