CLTC

clathrin heavy chain, the group of Clathrin subunits

Basic information

Region (hg38): 17:59619683-59696956

Previous symbols: [ "CLTCL2" ]

Links

ENSG00000141367 ∙ NCBI:1213 ∙ OMIM:118955 ∙ HGNC:2092 ∙ Uniprot:Q00610 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 56 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 56	AD	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; Musculoskeletal; Neurologic	26822784; 29100083; 31961069

ClinVar

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

• not provided (591 variants)
• Intellectual disability, autosomal dominant 56 (52 variants)
• Inborn genetic diseases (28 variants)
• CLTC-related condition (7 variants)
• not specified (3 variants)
• CLTC-Related Disorder (1 variants)
• Global developmental delay (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• See cases (1 variants)
• Intellectual disability (1 variants)
• Autosomal dominant non-syndromic intellectual disability;Intellectual disability, autosomal dominant 56 (1 variants)
• Abnormal corpus callosum morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLTC 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			7	164	12	183
missense	2	5	223	1		231
nonsense	15	8	1			24
start loss						0
frameshift	15	12	1			28
inframe indel	2	3	6			11
splice donor/acceptor (+/-2bp)	1	6				7
splice region	2		30	30	11	73
non coding		1	5	82	9	97
Total	35	35	243	247	21

Highest pathogenic variant AF is 0.00000658

Variants in CLTC

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

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

Position	Type	Phenotype	Significance	ClinVar
17-59620135-G-C			Uncertain significance (Apr 24, 2023)
17-59620149-A-C			Benign/Likely benign (Jan 01, 2024)
17-59620153-C-G			Uncertain significance (Aug 10, 2022)
17-59620155-T-C			Likely benign (Apr 28, 2022)
17-59620158-T-C			Likely benign (Jul 17, 2023)
17-59620161-G-A			Likely benign (Dec 27, 2022)
17-59620177-C-A			Uncertain significance (Dec 22, 2022)
17-59620182-G-A			Likely benign (May 07, 2022)
17-59620183-GGCCCGGGCTGGTGAGGGCTGT-G			Uncertain significance (Apr 24, 2021)
17-59620185-C-A			Likely benign (Jun 29, 2022)
17-59620186-C-A			Likely benign (Oct 03, 2023)
17-59620190-G-A			Uncertain significance (Oct 03, 2023)
17-59644258-T-A			Likely benign (Oct 27, 2022)
17-59644259-C-A			Benign (Dec 13, 2023)
17-59644262-A-C			Likely benign (Dec 14, 2022)
17-59644263-T-C			Likely benign (Jul 23, 2022)
17-59644276-C-G			Uncertain significance (Mar 25, 2022)
17-59644285-C-T			Likely benign (Feb 21, 2023)
17-59644295-A-G			Uncertain significance (Apr 06, 2022)
17-59644296-C-T			Likely benign (Nov 10, 2022)
17-59644311-C-G			Likely benign (Dec 11, 2023)
17-59644320-C-T		CLTC-related disorder	Benign/Likely benign (Mar 01, 2024)
17-59644321-C-T			Conflicting classifications of pathogenicity (Feb 01, 2024)
17-59644330-G-T			Pathogenic (Mar 19, 2022)
17-59644343-TC-T		Intellectual disability, autosomal dominant 56	Likely pathogenic (Jan 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLTC	protein_coding	protein_coding	ENST00000269122	32	76453

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.09e-12	125714	0	26	125740	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	7.76	251	910	0.276	0.0000487	11088
Missense in Polyphen		61	376.62	0.16197		4984
Synonymous	1.63	276	313	0.882	0.0000159	3142
Loss of Function	8.31	4	88.2	0.0453	0.00000457	1059

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000475	0.000475
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000799	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000364	0.0000327
Other	0.00	0.00

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. Acts as component of the TACC3/ch- TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter- microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). {ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}.
• Disease: DISEASE: Mental retardation, autosomal dominant 56 (MRD56) [MIM:617854]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26822784, ECO:0000269|PubMed:29100083}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;VEGFA-VEGFR2 Signaling Pathway;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Developmental Biology;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Signaling by WNT;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;Membrane Trafficking;Entry of Influenza Virion into Host Cell via Endocytosis;Influenza Life Cycle;Influenza Infection;MHC class II antigen presentation;TCR;Infectious disease;Immune System;LDL clearance;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Adaptive Immune System;Retrograde neurotrophin signalling;Transport of small molecules;CRH;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);WNT5A-dependent internalization of FZD4;PCP/CE pathway;Signaling by NTRKs;EGFR1;Beta-catenin independent WNT signaling;Plasma lipoprotein assembly, remodeling, and clearance;Cargo recognition for clathrin-mediated endocytosis;Arf6 trafficking events;L1CAM interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;FAS (CD95) signaling pathway (Consensus)

Recessive Scores

• pRec: 0.946

Intolerance Scores

• loftool: 0.190
• rvis_EVS: -1.31
• rvis_percentile_EVS: 4.85

Haploinsufficiency Scores

• pHI: 0.647
• hipred: Y
• hipred_score: 0.729
• ghis: 0.661

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cltc

Zebrafish Information Network

• Gene name: cltca
• Affected structure: caudal vein plexus
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: mitotic cell cycle;osteoblast differentiation;intracellular protein transport;receptor-mediated endocytosis;autophagy;antigen processing and presentation of exogenous peptide antigen via MHC class II;receptor internalization;low-density lipoprotein particle receptor catabolic process;transferrin transport;low-density lipoprotein particle clearance;retrograde transport, endosome to Golgi;transcytosis;clathrin coat assembly;cell division;Wnt signaling pathway, planar cell polarity pathway;regulation of mitotic spindle organization;membrane organization;clathrin-dependent endocytosis;negative regulation of hyaluronan biosynthetic process;negative regulation of protein localization to plasma membrane
• Cellular component: lysosome;endosome;spindle;cytosol;plasma membrane;focal adhesion;membrane;clathrin coat;clathrin coat of trans-Golgi network vesicle;clathrin coat of coated pit;clathrin-coated vesicle;clathrin-coated endocytic vesicle membrane;trans-Golgi network membrane;protein-containing complex;endolysosome membrane;melanosome;intracellular membrane-bounded organelle;clathrin-coated endocytic vesicle;extracellular exosome;clathrin complex;mitotic spindle;extracellular vesicle;mitotic spindle microtubule
• Molecular function: RNA binding;double-stranded RNA binding;structural molecule activity;protein binding;protein kinase binding;clathrin light chain binding;low-density lipoprotein particle receptor binding;disordered domain specific binding;ubiquitin-specific protease binding