TTC7A

tetratricopeptide repeat domain 7A, the group of Tetratricopeptide repeat domain containing|PI4KA lipid kinase complex

Basic information

Region (hg38): 2:46915868-47076137

Previous symbols: [ "TTC7" ]

Links

ENSG00000068724 ∙ NCBI:57217 ∙ OMIM:609332 ∙ HGNC:19750 ∙ Uniprot:Q9ULT0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• gastrointestinal defects and immunodeficiency syndrome 1 (Definitive), mode of inheritance: AR
• multiple intestinal atresia (Strong), mode of inheritance: AR
• gastrointestinal defects and immunodeficiency syndrome 1 (Strong), mode of inheritance: AR
• multiple intestinal atresia (Supportive), mode of inheritance: AR
• multiple intestinal atresia (Supportive), mode of inheritance: AR
• multiple intestinal atresia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gastrointestinal defects and immunodeficiency syndrome 1	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	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal	23423984; 25174867
HSCT has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTC7A gene.

• Multiple gastrointestinal atresias (755 variants)
• not provided (163 variants)
• Inborn genetic diseases (60 variants)
• not specified (33 variants)
• Gastrointestinal defects and immunodeficiency syndrome 1 (30 variants)
• Gastrointestinal defect and immunodeficiency syndrome (8 variants)
• TTC7A-related condition (4 variants)
• Common variable immunodeficiency (2 variants)
• Severe combined immunodeficiency disease (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 TTC7A 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	168	15	185
missense		3	356	13	6	378
nonsense	14	4	2			20
start loss						0
frameshift	11	9				20
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	9				12
splice region	1	2	22	36		61
non coding			1	102	91	194
Total	28	25	363	283	112

Highest pathogenic variant AF is 0.0000329

Variants in TTC7A

This is a list of pathogenic ClinVar variants found in the TTC7A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-46916850-G-A			Benign (Jul 09, 2018)
2-46917031-A-C			Benign (Jul 10, 2018)
2-46917064-C-G			Benign (Jul 09, 2018)
2-46917202-C-T			Uncertain significance (Apr 13, 2021)
2-46917210-G-A			Likely benign (Feb 01, 2023)
2-46917239-C-T			Likely benign (Jan 01, 2024)
2-46917255-C-G		TTC7A-related disorder	Benign/Likely benign (Mar 06, 2019)
2-46917393-T-C			Benign (Jul 06, 2018)
2-46917490-A-G			Benign (Jul 06, 2018)
2-46940847-T-C			Benign (Jul 09, 2018)
2-46940931-A-G			Benign (Jul 09, 2018)
2-46941188-C-A			Benign (Jul 06, 2018)
2-46941458-C-A			Benign (Jul 06, 2018)
2-46941548-GC-G		Gastrointestinal defect and immunodeficiency syndrome	Likely pathogenic (Apr 04, 2023)
2-46941553-G-A		Multiple gastrointestinal atresias	Likely benign (Oct 05, 2019)
2-46941553-G-T		Multiple gastrointestinal atresias	Uncertain significance (Jul 29, 2020)
2-46941556-C-T		Multiple gastrointestinal atresias	Likely benign (May 09, 2022)
2-46941562-C-T		Multiple gastrointestinal atresias	Likely benign (Feb 28, 2023)
2-46941568-C-T		Multiple gastrointestinal atresias	Likely benign (Dec 01, 2023)
2-46941570-A-T		Multiple gastrointestinal atresias	Uncertain significance (May 20, 2023)
2-46941571-C-T		not specified	Likely benign (Feb 04, 2024)
2-46941572-C-T			Likely benign (May 01, 2022)
2-46941573-T-C		TTC7A-related disorder	Uncertain significance (May 11, 2023)
2-46941576-A-G		Multiple gastrointestinal atresias	Uncertain significance (Dec 15, 2021)
2-46941577-G-A		Multiple gastrointestinal atresias	Likely benign (Aug 07, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTC7A	protein_coding	protein_coding	ENST00000319190	20	159981

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.54e-31	0.0000332	125638	0	110	125748	0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.775	570	520	1.10	0.0000314	5553
Missense in Polyphen		150	149.69	1.0021		1578
Synonymous	-0.0844	231	229	1.01	0.0000146	1706
Loss of Function	-0.0466	47	46.7	1.01	0.00000230	516

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000505	0.000489
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000512	0.000510
Middle Eastern	0.000505	0.000489
South Asian	0.000265	0.000261
Other	0.000503	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and FAM126A, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}.

Recessive Scores

• pRec: 0.100

Intolerance Scores

• loftool: 0.832
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.18

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.250
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.256

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttc7
• Phenotype: immune system phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; pigmentation phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: cellular iron ion homeostasis;hemopoiesis;phosphatidylinositol phosphorylation;protein localization to plasma membrane
• Cellular component: cytoplasm;plasma membrane