CLHC1

Summary

CLHC1 (clathrin heavy chain linker domain containing 1, HGNC:26453) is a protein-coding gene on chromosome 2p16.1, encoding Clathrin heavy chain linker domain-containing protein 1 (Q8NHS4).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 121 total — 1 likely-pathogenic
• MANE Select transcript: NM_152385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26453
Approved symbol	CLHC1
Name	clathrin heavy chain linker domain containing 1
Location	2p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31438
Ensembl gene	ENSG00000162994
Ensembl biotype	protein_coding
Entrez	130162

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000401408, ENST00000403506, ENST00000406076, ENST00000407122, ENST00000411884, ENST00000425841, ENST00000428621, ENST00000451916, ENST00000463300, ENST00000464243, ENST00000466020, ENST00000487320, ENST00000494539, ENST00000888022, ENST00000939099

RefSeq mRNA: 10 — MANE Select: NM_152385 NM_001135598, NM_001353779, NM_001353780, NM_001353781, NM_001353782, NM_001353783, NM_001353784, NM_001353786, NM_001353787, NM_152385

CCDS: CCDS33201, CCDS46287

Canonical transcript exons

ENST00000401408 — 13 exons

Exon	Start	End
ENSE00001209963	55209404	55209516
ENSE00001209968	55209630	55209831
ENSE00001210140	55232223	55232293
ENSE00001354320	55228032	55228204
ENSE00001507215	55208626	55208710
ENSE00003504601	55206270	55206376
ENSE00003538899	55222235	55222493
ENSE00003556496	55212673	55212806
ENSE00003565703	55177602	55177781
ENSE00003653793	55217811	55217998
ENSE00003673172	55180510	55180712
ENSE00003694057	55181570	55181744
ENSE00003842411	55172547	55175986

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 94.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2064 / max 133.3829, expressed in 1602 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28444	5.4406	1550
28445	0.5313	282
28446	0.1506	68
28448	0.0435	13
28447	0.0403	9

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.21	gold quality
sperm	CL:0000019	90.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.11	gold quality
bronchial epithelial cell	CL:0002328	87.17	gold quality
ventricular zone	UBERON:0003053	86.90	gold quality
adrenal tissue	UBERON:0018303	86.88	gold quality
adenohypophysis	UBERON:0002196	86.60	gold quality
lower esophagus mucosa	UBERON:0035834	86.56	gold quality
calcaneal tendon	UBERON:0003701	86.11	gold quality
bronchus	UBERON:0002185	85.09	gold quality
pituitary gland	UBERON:0000007	84.91	gold quality
left testis	UBERON:0004533	83.70	gold quality
left lobe of thyroid gland	UBERON:0001120	83.47	gold quality
right ovary	UBERON:0002118	83.37	gold quality
ganglionic eminence	UBERON:0004023	83.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.29	gold quality
right lobe of thyroid gland	UBERON:0001119	83.27	gold quality
right testis	UBERON:0004534	83.20	gold quality
right adrenal gland cortex	UBERON:0035827	83.12	gold quality
left ovary	UBERON:0002119	82.88	gold quality
body of uterus	UBERON:0009853	82.65	gold quality
body of pancreas	UBERON:0001150	82.45	gold quality
thyroid gland	UBERON:0002046	82.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.37	gold quality
testis	UBERON:0000473	82.34	gold quality
cortical plate	UBERON:0005343	81.81	gold quality
right adrenal gland	UBERON:0001233	81.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.14	gold quality
left adrenal gland cortex	UBERON:0035825	80.91	gold quality
stromal cell of endometrium	CL:0002255	80.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

105 targeting CLHC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clhc1	ENSMUSG00000020461
rattus_norvegicus	Clhc1	ENSRNOG00000004456
drosophila_melanogaster	Chc	FBGN0000319
caenorhabditis_elegans		WBGENE00011867

Paralogs (2): CLTCL1 (ENSG00000070371), CLTC (ENSG00000141367)

Protein

Protein identifiers

Clathrin heavy chain linker domain-containing protein 1 — Q8NHS4 (reviewed: Q8NHS4)

All UniProt accessions (6): B5MC48, C9J143, E7EQP3, E7EVC5, Q8NHS4, H7C1D8

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NHS4-1	1	yes
Q8NHS4-2	2

RefSeq proteins (10): NP_001129070, NP_001340708, NP_001340709, NP_001340710, NP_001340711, NP_001340712, NP_001340713, NP_001340715, NP_001340716, NP_689598* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012331	Clathrin_H-chain_linker	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017212	CLHC1	Family
IPR032755	TSNAXIP1_N	Domain

Pfam: PF13838, PF15739

UniProt features (7 total): sequence variant 4, chain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHS4-F1	81.85	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): AREB6_01, AACYNNNNTTCCS_UNKNOWN, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, TCCCRNNRTGC_UNKNOWN, ASH1L_TARGET_GENES, ATF5_TARGET_GENES, CSHL1_TARGET_GENES, DLX6_TARGET_GENES, ELF2_TARGET_GENES, FEV_TARGET_GENES, HMGA1_TARGET_GENES, HOXB4_TARGET_GENES, HOXC6_TARGET_GENES, IRF5_TARGET_GENES, NCOA2_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLHC1	ENKD1	Q9H0I2	555
CLHC1	SCRN1	Q12765	521
CLHC1	ZDHHC19	Q8WVZ1	492
CLHC1	LUZP2	Q86TE4	489
CLHC1	MATCAP2	Q8NCT3	475
CLHC1	ANKRD55	Q3KP44	454
CLHC1	C16orf95	Q9H693	446
CLHC1	SMIM21	Q3B7S5	434
CLHC1	ZNF621	Q6ZSS3	432
CLHC1	FAM120AOS	Q5T036	430
CLHC1	WDR93	Q6P2C0	419
CLHC1	ZNF136	P52737	419
CLHC1	CALY	Q9NYX4	410
CLHC1	TMEM129	A0AVI4	397
CLHC1	FERRY3	Q9NQ89	393
CLHC1	AKAP8	O43823	393

IntAct

11 interactions, top by confidence:

A	B	Type	Score
LMO2	CLHC1	psi-mi:“MI:0915”(physical association)	0.560
CEP170P1	CLHC1	psi-mi:“MI:0915”(physical association)	0.560
SGF29	CLHC1	psi-mi:“MI:0915”(physical association)	0.560
CLHC1	CEP170P1	psi-mi:“MI:0915”(physical association)	0.560
CLHC1	LMO2	psi-mi:“MI:0915”(physical association)	0.560
CLHC1	SGF29	psi-mi:“MI:0915”(physical association)	0.560
CLHC1	rep	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (10): CLHC1 (Two-hybrid), CLHC1 (Two-hybrid), CEP170P1 (Two-hybrid), CLHC1 (Affinity Capture-RNA), CLHC1 (Biochemical Activity), CLHC1 (Affinity Capture-MS), CLHC1 (Affinity Capture-MS), CLHC1 (Affinity Capture-RNA), CLHC1 (Two-hybrid), CLHC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0A5F8MPE6, A1A535, A8QHQ0, B0W730, O23463, O46470, O54829, O64851, O82645, P49758, P49802, P49803, P49809, Q058N0, Q0VA04, Q14D04, Q28IH8, Q4R6I5, Q4R7Z7, Q502W7, Q569B9, Q5PQS3, Q5SPP5, Q5XG48, Q5XIR8, Q641A2, Q6ZQ18, Q7T0S7, Q86VD1, Q8BG67, Q8BMD7, Q8CDN8, Q8H1E8, Q8IGJ0, Q8N957, Q8NCR3, Q8NHS4, Q96L03, Q96LI9

Diamond homologs: Q4R6I5, Q5M6W3, Q5XIR8, Q8NHS4, P11442, P49951, Q00610, Q68FD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

121 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	98
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
183280	NM_152385.4(CLHC1):c.1145G>A (p.Arg382Gln)	Likely pathogenic

SpliceAI

2572 predictions. Top by Δscore:

Variant	Effect	Δscore
2:55177597:CTTA:C	donor_loss	1.0000
2:55177598:TTA:T	donor_loss	1.0000
2:55177599:TACCT:T	donor_loss	1.0000
2:55177600:A:T	donor_loss	1.0000
2:55177601:C:CA	donor_loss	1.0000
2:55177601:CCTAT:C	donor_gain	1.0000
2:55177686:C:CT	acceptor_gain	1.0000
2:55206401:CAT:C	acceptor_gain	1.0000
2:55206403:T:TC	acceptor_gain	1.0000
2:55208656:T:TA	donor_gain	1.0000
2:55209517:C:CC	acceptor_gain	1.0000
2:55209620:A:C	donor_gain	1.0000
2:55209623:T:TA	donor_gain	1.0000
2:55209628:A:AC	donor_gain	1.0000
2:55209629:C:CC	donor_gain	1.0000
2:55209634:A:C	donor_gain	1.0000
2:55209744:G:C	donor_gain	1.0000
2:55209827:CATGC:C	acceptor_gain	1.0000
2:55209829:TGC:T	acceptor_gain	1.0000
2:55209829:TGCC:T	acceptor_loss	1.0000
2:55209830:GCCT:G	acceptor_loss	1.0000
2:55209832:C:CC	acceptor_gain	1.0000
2:55209832:CT:C	acceptor_loss	1.0000
2:55209833:T:A	acceptor_loss	1.0000
2:55232106:G:GT	donor_gain	1.0000
2:55232109:G:GG	donor_gain	1.0000
2:55175937:CTTTT:C	acceptor_gain	0.9900
2:55175987:C:CC	acceptor_gain	0.9900
2:55177600:A:AC	donor_gain	0.9900
2:55177601:C:CC	donor_gain	0.9900

AlphaMissense

3894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:55181586:A:G	W389R	0.974
2:55181586:A:T	W389R	0.974
2:55181594:A:T	V386D	0.968
2:55181634:C:G	G373R	0.966
2:55181634:C:T	G373R	0.966
2:55180627:C:G	A423P	0.961
2:55217951:T:A	K75N	0.959
2:55217951:T:G	K75N	0.959
2:55180626:G:T	A423D	0.958
2:55180690:C:A	G402W	0.956
2:55175936:A:G	W539R	0.955
2:55175936:A:T	W539R	0.955
2:55181606:C:G	R382P	0.952
2:55206316:A:C	S320R	0.950
2:55206316:A:T	S320R	0.950
2:55206318:T:G	S320R	0.950
2:55181621:C:T	G377E	0.944
2:55181633:C:T	G373E	0.944
2:55175915:A:G	C546R	0.941
2:55180689:C:T	G402E	0.940
2:55181618:A:G	L378S	0.934
2:55181622:C:G	G377R	0.931
2:55181622:C:T	G377R	0.931
2:55175924:C:G	A543P	0.924
2:55181582:A:T	V390D	0.924
2:55222241:A:C	F57L	0.923
2:55222241:A:T	F57L	0.923
2:55222243:A:G	F57L	0.923
2:55206335:G:T	A314D	0.922
2:55209774:A:G	L186P	0.922

dbSNP variants (sampled 300 via entrez): RS1000004442 (2:55225614 C>T), RS1000042922 (2:55233105 G>A), RS1000074323 (2:55233227 A>G,T), RS1000115493 (2:55196918 G>A,C), RS1000149447 (2:55232796 C>T), RS1000157806 (2:55222968 C>A,G), RS1000250750 (2:55178768 G>A,T), RS1000256217 (2:55217749 T>C), RS1000257356 (2:55191555 G>A), RS1000297079 (2:55228758 T>A,G), RS1000369081 (2:55217211 A>G), RS1000391704 (2:55181137 T>A), RS1000429465 (2:55172801 T>C), RS1000439078 (2:55223133 G>T), RS1000462233 (2:55186714 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1972	Metabolite levels	9.000000e-06
GCST012047_14	Fasting glucose	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010541	trimethylamine-N-oxide measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
Cyclosporine	increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
avobenzone	decreases expression	1
jinfukang	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Oxyquinoline	decreases expression	1
Aflatoxin B1	increases methylation	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.