CCDC158

Summary

CCDC158 (coiled-coil domain containing 158, HGNC:26374) is a protein-coding gene on chromosome 4q21.1, encoding Coiled-coil domain-containing protein 158 (Q5M9N0). Plays a role in receptor-mediated endocytosis in proximal tubular cells of the kidney.

At a glance

• Gene–disease (curated): renal tubule disorder (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 190 total
• MANE Select transcript: NM_001394954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26374
Approved symbol	CCDC158
Name	coiled-coil domain containing 158
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25770
Ensembl gene	ENSG00000163749
Ensembl biotype	protein_coding
OMIM	621144
Entrez	339965

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000388914, ENST00000434846, ENST00000504667, ENST00000504868, ENST00000509851, ENST00000682701

RefSeq mRNA: 2 — MANE Select: NM_001394954 NM_001042784, NM_001394954

CCDS: CCDS43242, CCDS93551

Canonical transcript exons

ENST00000682701 — 25 exons

Exon	Start	End
ENSE00001077897	76383662	76383738
ENSE00001077899	76384088	76384415
ENSE00001077901	76379290	76379404
ENSE00001077902	76353123	76353281
ENSE00001077903	76382610	76382720
ENSE00001077908	76351720	76351812
ENSE00001504385	76367294	76367776
ENSE00001504387	76369426	76369623
ENSE00001504388	76371417	76371536
ENSE00002085916	76412090	76412132
ENSE00003478135	76355324	76355436
ENSE00003483217	76396269	76396486
ENSE00003534731	76325857	76326015
ENSE00003570998	76328900	76328967
ENSE00003579651	76362126	76362315
ENSE00003594220	76384556	76384665
ENSE00003603730	76323302	76323409
ENSE00003624684	76331344	76331403
ENSE00003625744	76350996	76351121
ENSE00003627138	76332432	76332491
ENSE00003671469	76357374	76357526
ENSE00003916117	76334010	76334167
ENSE00003917074	76313039	76313246
ENSE00003919006	76420965	76421141
ENSE00003920445	76403138	76403280

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 98.12.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.12	gold quality
left testis	UBERON:0004533	89.74	gold quality
right testis	UBERON:0004534	89.26	gold quality
testis	UBERON:0000473	87.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.63	gold quality
islet of Langerhans	UBERON:0000006	73.68	gold quality
right coronary artery	UBERON:0001625	72.53	gold quality
buccal mucosa cell	CL:0002336	70.95	silver quality
cortical plate	UBERON:0005343	69.99	gold quality
descending thoracic aorta	UBERON:0002345	68.04	gold quality
left coronary artery	UBERON:0001626	67.94	gold quality
coronary artery	UBERON:0001621	66.80	gold quality
sural nerve	UBERON:0015488	66.69	gold quality
tibial artery	UBERON:0007610	66.63	gold quality
popliteal artery	UBERON:0002250	66.61	gold quality
aorta	UBERON:0000947	66.27	gold quality
ascending aorta	UBERON:0001496	66.23	gold quality
thoracic aorta	UBERON:0001515	66.16	gold quality
calcaneal tendon	UBERON:0003701	66.10	gold quality
adult organism	UBERON:0007023	65.54	gold quality
right lobe of liver	UBERON:0001114	64.89	gold quality
mucosa of stomach	UBERON:0001199	64.71	gold quality
left lobe of thyroid gland	UBERON:0001120	64.10	gold quality
pancreas	UBERON:0001264	63.66	gold quality
right lobe of thyroid gland	UBERON:0001119	63.41	gold quality
thyroid gland	UBERON:0002046	63.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.56	gold quality
prefrontal cortex	UBERON:0000451	61.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting CCDC158, 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-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6780A-3P	98.42	67.49	1518

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc158	ENSMUSG00000050050
rattus_norvegicus	Ccdc158	ENSRNOG00000002204

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Coiled-coil domain-containing protein 158 — Q5M9N0 (reviewed: Q5M9N0)

All UniProt accessions (2): A0A804HIY6, Q5M9N0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in receptor-mediated endocytosis in proximal tubular cells of the kidney.

Subunit / interactions. Interacts with clathrin and RAB5.

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle. Early endosome.

Tissue specificity. Expressed in testis and kidney. Expressed in testis. Expressed in testis and kidney.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5M9N0-1	1	yes
Q5M9N0-2	2
Q5M9N0-3	3

RefSeq proteins (2): NP_001036249, NP_001381883* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031809	CCDC158	Family

Pfam: PF15921

UniProt features (20 total): compositionally biased region 7, region of interest 3, splice variant 3, sequence variant 3, coiled-coil region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5M9N0-F1	73.43	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, GOCC_CLATHRIN_COATED_VESICLE, chr4q21, GOMF_CLATHRIN_BINDING, GOBP_RECEPTOR_MEDIATED_ENDOCYTOSIS, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, HMGA1_TARGET_GENES, MAFG_TARGET_GENES, MIR12136, MIR23A_3P_MIR23B_3P, MIR23C, MIR4477A

GO Biological Process (1): receptor-mediated endocytosis (GO:0006898)

GO Molecular Function (2): clathrin binding (GO:0030276), protein binding (GO:0005515)

GO Cellular Component (2): early endosome (GO:0005769), clathrin-coated vesicle (GO:0030136)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endocytosis	1
protein binding	1
binding	1
endosome	1
coated vesicle	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC158	TMEM236	Q5W0B7	531
CCDC158	TXLNB	Q8N3L3	516
CCDC158	NUP54	Q7Z3B4	505
CCDC158	NCLN	Q969V3	490
CCDC158	HELQ	Q8TDG4	466
CCDC158	PAFAH2	Q99487	459
CCDC158	DNAAF8	Q8IYS4	448
CCDC158	PPEF2	O14830	447
CCDC158	SDAD1	Q9NVU7	420
CCDC158	ZNF615	Q8N8J6	419
CCDC158	MASTL	Q96GX5	418
CCDC158	TBC1D12	O60347	416
CCDC158	ALMS1	Q8TCU4	411
CCDC158	FAM47E	Q6ZV65	407
CCDC158	PPP6R3	Q5H9R7	403

IntAct

18 interactions, top by confidence:

A	B	Type	Score
GPSM1	CCDC158	psi-mi:“MI:0915”(physical association)	0.550
CCDC158	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
CCDC158	SLC3A2	psi-mi:“MI:0915”(physical association)	0.400
CCDC158	SCGB2A1	psi-mi:“MI:0915”(physical association)	0.400
CCDC158	ANKFY1	psi-mi:“MI:0915”(physical association)	0.400
CCDC158	USP20	psi-mi:“MI:0915”(physical association)	0.400
CCDC158	USP33	psi-mi:“MI:0915”(physical association)	0.400
FCHSD2	CCDC158	psi-mi:“MI:0915”(physical association)	0.370
SH3GLB2	CCDC158	psi-mi:“MI:0915”(physical association)	0.370
SGF29	CCDC158	psi-mi:“MI:0915”(physical association)	0.370
NAGK	CCDC158	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CBX2	TRANK1	psi-mi:“MI:0914”(association)	0.350
CBX4		psi-mi:“MI:0914”(association)	0.350
CCDC158	FOS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): CCDC158 (Two-hybrid), MYCBP2 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), SCGB2A1 (Affinity Capture-MS), GPSM1 (Two-hybrid), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), CCDC158 (Two-hybrid), TBC1D21 (Two-hybrid), UBQLN2 (Two-hybrid)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z8P9, A6QR54, B4KE73, E9Q7G0, F1R4Y7, O15083, O55156, O60437, O61308, Q11102, Q13439, Q15643, Q3SWS9, Q5DTN8, Q5M9N0, Q5PQ23, Q5RI56, Q5U4E6, Q5VZ66, Q5ZKK5, Q66H89, Q6DFL0, Q6PH08, Q6ZU80, Q7ZW57, Q811U3, Q8BI22, Q8BVL9, Q8CDI6, Q8CDI7, Q8CGB3, Q8HYY4, Q8IUD2, Q8K3M6, Q8WXW3, Q91VW5, Q96AA8, Q96N16

Diamond homologs: Q5M9N0, Q8CDI6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	171
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3977 predictions. Top by Δscore:

Variant	Effect	Δscore
4:76333983:T:A	donor_gain	1.0000
4:76334009:CA:C	donor_gain	1.0000
4:76334021:CAAGG:C	donor_gain	1.0000
4:76334042:T:TA	donor_gain	1.0000
4:76334049:T:TA	donor_gain	1.0000
4:76350991:CT:C	donor_loss	1.0000
4:76350994:A:AC	donor_gain	1.0000
4:76350994:AC:A	donor_loss	1.0000
4:76350995:C:CC	donor_gain	1.0000
4:76350995:CA:C	donor_gain	1.0000
4:76350995:CAT:C	donor_gain	1.0000
4:76350995:CATG:C	donor_gain	1.0000
4:76351117:AGTTC:A	acceptor_gain	1.0000
4:76351118:GTTC:G	acceptor_gain	1.0000
4:76351119:TTC:T	acceptor_gain	1.0000
4:76351120:TC:T	acceptor_gain	1.0000
4:76351120:TCC:T	acceptor_loss	1.0000
4:76351121:CC:C	acceptor_gain	1.0000
4:76351122:C:CA	acceptor_loss	1.0000
4:76351122:C:CC	acceptor_gain	1.0000
4:76351718:A:AC	donor_gain	1.0000
4:76351719:C:CC	donor_gain	1.0000
4:76353118:ATTAC:A	donor_loss	1.0000
4:76353120:TA:T	donor_loss	1.0000
4:76353139:T:TA	donor_gain	1.0000
4:76353277:TTCTC:T	acceptor_gain	1.0000
4:76353279:CTC:C	acceptor_gain	1.0000
4:76353281:CCTA:C	acceptor_loss	1.0000
4:76353282:C:CC	acceptor_gain	1.0000
4:76353283:T:C	acceptor_loss	1.0000

AlphaMissense

7382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:76355373:A:G	L746P	1.000
4:76355390:T:A	R740S	1.000
4:76355390:T:G	R740S	1.000
4:76355393:T:A	K739N	1.000
4:76355393:T:G	K739N	1.000
4:76355398:C:G	A738P	1.000
4:76313231:A:C	I1094S	0.999
4:76313231:A:G	I1094T	0.999
4:76323340:A:G	L1076S	0.999
4:76323349:A:G	L1073P	0.999
4:76355377:C:G	A745P	0.999
4:76355403:A:C	I736S	0.999
4:76355403:A:G	I736T	0.999
4:76355411:T:A	Q733H	0.999
4:76355411:T:G	Q733H	0.999
4:76355415:A:C	M732R	0.999
4:76355415:A:G	M732T	0.999
4:76355424:G:T	A729E	0.999
4:76355425:C:G	A729P	0.999
4:76313231:A:T	I1094N	0.998
4:76323331:A:G	L1079P	0.998
4:76351742:A:G	L839P	0.998
4:76355370:T:G	Q747P	0.998
4:76355382:A:T	I743K	0.998
4:76355391:C:A	R740I	0.998
4:76355391:C:G	R740T	0.998
4:76355394:T:A	K739I	0.998
4:76355395:T:C	K739E	0.998
4:76355403:A:T	I736N	0.998
4:76355412:T:G	Q733P	0.998

dbSNP variants (sampled 300 via entrez): RS1000003967 (4:76420591 G>A), RS1000021944 (4:76354551 G>A), RS1000024359 (4:76423121 C>A), RS1000039166 (4:76408477 G>A), RS10000618 (4:76390715 A>G,T), RS10000821 (4:76387217 G>A,C), RS1000117049 (4:76415406 G>C), RS10001182 (4:76400104 C>T), RS10001396 (4:76329354 C>A,G,T), RS10002302 (4:76395987 T>C), RS10002448 (4:76348109 G>A,C), RS1000252751 (4:76380403 T>G), RS10002558 (4:76390318 T>C,G), RS1000260270 (4:76338937 A>G), RS1000272263 (4:76377879 A>G)

Disease associations

OMIM: gene MIM:621144 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
renal tubule disorder	Limited	Autosomal recessive

Mondo (1): renal tubule disorder (MONDO:0021568)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000649_16	Chronic kidney disease	1.000000e-19
GCST004412_8	Craniofacial microsomia	8.000000e-08
GCST007876_84	Estimated glomerular filtration rate	2.000000e-72
GCST009391_511	Metabolite levels	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010527	pyridoxate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Estradiol	affects binding, increases reaction	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02256579	Not specified	UNKNOWN	Utility of Urinary beta2 Microglobulin as an Early Marker of Renal Dysfunction in Vietnamese HIV-Infected Patients
NCT03253614	Not specified	COMPLETED	Auditive and Renal Long Term Outcomes - Risk After Aminoglycoside Therapy in Neonates (AURORA)