CLTCL1

clathrin heavy chain like 1, the group of Clathrin subunits

Basic information

Region (hg38): 22:19179472-19291719

Previous symbols: [ "CLTCL" ]

Links

ENSG00000070371 ∙ NCBI:8218 ∙ OMIM:601273 ∙ HGNC:2093 ∙ Uniprot:P53675 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital insensitivity to pain with severe intellectual disability (Supportive), mode of inheritance: AR
• multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLTCL1 gene.

• Inborn genetic diseases (69 variants)
• not provided (47 variants)
• not specified (3 variants)
• CLTCL1-related condition (1 variants)
• Autism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLTCL1 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				6	7	13
missense		1	71	10	9	91
nonsense			2			2
start loss			1			1
frameshift				1	2	3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				3	2	5
non coding					1	1
Total	0	1	75	17	19

Highest pathogenic variant AF is 0.000505

Variants in CLTCL1

This is a list of pathogenic ClinVar variants found in the CLTCL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-19180764-C-T		not specified	Uncertain significance (Dec 15, 2022)
22-19180775-C-T			Benign (Feb 01, 2023)
22-19183415-T-C		not specified	Uncertain significance (Feb 15, 2023)
22-19183443-C-G			Benign (Dec 31, 2019)
22-19183443-C-T			Benign (Apr 19, 2019)
22-19183471-C-T		CLTCL1-related disorder	Likely benign (Nov 08, 2023)
22-19183486-AAGCAGGTCAT-A			Benign (Dec 31, 2019)
22-19183518-C-T		not specified	Uncertain significance (Oct 06, 2021)
22-19183540-C-G		not specified	Uncertain significance (Aug 04, 2022)
22-19183561-C-CT			Likely benign (Dec 31, 2019)
22-19183570-C-T		CLTCL1-related disorder	Likely benign (Feb 18, 2020)
22-19183580-T-C		not specified	Uncertain significance (Jul 09, 2021)
22-19187611-T-A		not specified	Uncertain significance (Feb 22, 2023)
22-19187649-A-G		not specified	Uncertain significance (Nov 30, 2021)
22-19187701-C-G		not specified	Uncertain significance (Jun 21, 2021)
22-19187701-C-T		not specified	Uncertain significance (Dec 28, 2022)
22-19187727-C-G			Likely benign (Nov 09, 2018)
22-19187974-C-T			Likely benign (Nov 01, 2022)
22-19188019-C-T		not specified	Uncertain significance (Aug 13, 2021)
22-19188067-G-A		not specified	Uncertain significance (Aug 17, 2022)
22-19188083-C-G		not specified	Uncertain significance (Nov 27, 2023)
22-19188084-T-C			Uncertain significance (Sep 01, 2022)
22-19191342-G-A			Uncertain significance (Sep 29, 2016)
22-19191355-C-A		CLTCL1-related disorder	Likely benign (Feb 20, 2019)
22-19191396-A-G		not specified	Uncertain significance (Dec 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLTCL1	protein_coding	protein_coding	ENST00000263200	32	112254

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.51e-37	0.00333	1193	123631	13	124837	0.902

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.777	840	906	0.927	0.0000504	10770
Missense in Polyphen		303	344.83	0.87869		4438
Synonymous	0.765	336	354	0.948	0.0000205	3086
Loss of Function	1.68	66	82.5	0.800	0.00000393	978

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.03	1.94
Ashkenazi Jewish	1.01	0.919
East Asian	1.00	0.958
Finnish	1.00	0.956
European (Non-Finnish)	1.00	0.872
Middle Eastern	1.00	0.958
South Asian	1.00	0.960
Other	1.00	0.899

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network (By similarity). {ECO:0000250}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Endocytosis - Homo sapiens (human);Lysosome - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Synaptic Vesicle Pathway;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation (Consensus)

Recessive Scores

• pRec: 0.766

Intolerance Scores

• loftool: 1.00
• rvis_EVS: 2.35
• rvis_percentile_EVS: 98.42

Haploinsufficiency Scores

• pHI: 0.267
• hipred: N
• hipred_score: 0.219
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: mitotic cell cycle;intracellular protein transport;receptor-mediated endocytosis;anatomical structure morphogenesis;retrograde transport, endosome to Golgi;positive regulation of glucose import;clathrin coat assembly;membrane organization
• Cellular component: early endosome;late endosome;trans-Golgi network;spindle;cytosol;plasma membrane;clathrin-coated pit;membrane;clathrin coat of trans-Golgi network vesicle;coated vesicle;clathrin-coated vesicle;clathrin-coated endocytic vesicle;recycling endosome;extracellular exosome;clathrin complex;sorting endosome
• Molecular function: structural molecule activity;protein binding;clathrin light chain binding