CLTCL1

protein-coding

clathrin heavy chain like 1, the group of Clathrin subunits

Gene summary

This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

Previous symbols:

CLTCL

MANE transcript

NM_007098.4

Inheritance

AR, AD

ClinVar variants

P:1U:288B:68

Top phenotype

congenital insensitivity to pain with severe intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr22:19,179,473-19,291,719

External References & Databases

Ensembl (ENSG00000070371)

Transcript & Mutation Effects

hg38 • Region Span ~112.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital insensitivity to pain with severe intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018682

Submitter: Orphanet

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLTCL1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 274

not providedTotal: 89

CLTCL1-related disorderTotal: 22

AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007098.4. 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			6 clinvar	27 clinvar	4 clinvar	37
missense		1 clinvar	272 clinvar	21 clinvar	13 clinvar	307
nonsense			5 clinvar			5
start loss			1 clinvar			1
frameshift			1 clinvar	1 clinvar	2 clinvar	4
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	288	49	19	357

Highest pathogenic variant AF is 0.00063261023

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007098.4	RefSeq	NP_009029.3	32	MANE Select
ENST00000427926.6	Ensembl	ENSP00000441158.1	32	MANE Select
NM_001835.4	RefSeq	NP_001826.3	31	Standard
ENST00000449918.1	Ensembl	ENSP00000443264.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

mitotic cell cycle
intracellular protein transport
receptor-mediated endocytosis
anatomical structure morphogenesis
retrograde transport, endosome to Golgi

Molecular Function

structural molecule activity
protein binding
clathrin light chain binding

Cellular Component

early endosome
late endosome
trans-Golgi network
spindle
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263200
Coding exons: 32
Length: 112254
Individuals with no LoFs: 1193
Homozygous LoFs: 123631
Heterozygous LoFs: 13
Defined: 124837
p: 0.902

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.777	840	906	0.927	0.0000504	10770
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	1.0	0.91	notable
Latino/Admixed American	1.0	0.93	notable
Ashkenazi Jewish	1.0	0.92	notable
East Asian	1.0	0.96	notable
Finnish	1.0	0.96	notable
European (Non-Finnish)	1.0	0.87	notable
South Asian	1.0	0.96	notable
Other	1.0	0.90	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.766

Intolerance Scores

LoFtool: 1.00
RVIS EVS: 2.35
RVIS percentile EVS: 98.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.855

Gene Damage Prediction

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