C18orf63

Summary

C18orf63 (chromosome 18 open reading frame 63, HGNC:40037) is a protein-coding gene on chromosome 18q22.3, encoding Uncharacterized protein C18orf63 (Q68DL7).

At a glance

• Clinical variants (ClinVar): 23 total — 4 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001174123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40037
Approved symbol	C18orf63
Name	chromosome 18 open reading frame 63
Location	18q22.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP781G0119
Ensembl gene	ENSG00000206043
Ensembl biotype	protein_coding
Entrez	644041

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000579455

RefSeq mRNA: 1 — MANE Select: NM_001174123 NM_001174123

CCDS: CCDS54189

Canonical transcript exons

ENST00000579455 — 14 exons

Exon	Start	End
ENSE00001492945	74356481	74359189
ENSE00001492947	74354457	74354546
ENSE00001492948	74353246	74354268
ENSE00001492958	74342032	74342128
ENSE00001492959	74338715	74338824
ENSE00001492961	74330866	74330942
ENSE00001492962	74328995	74329036
ENSE00001492964	74327947	74328058
ENSE00001492965	74322698	74322754
ENSE00001492967	74320513	74320591
ENSE00001492968	74317834	74317999
ENSE00001505853	74343519	74343702
ENSE00001505854	74342241	74342326
ENSE00002696016	74315839	74316109

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 81.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0110 / max 12.6304, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170745	0.0078	3
170746	0.0032	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.18	gold quality
testis	UBERON:0000473	67.99	gold quality
right testis	UBERON:0004534	67.95	gold quality
left testis	UBERON:0004533	66.19	gold quality
quadriceps femoris	UBERON:0001377	64.14	gold quality
cerebellar vermis	UBERON:0004720	63.05	gold quality
thymus	UBERON:0002370	58.54	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.05	silver quality
sural nerve	UBERON:0015488	39.42	gold quality
skeletal muscle tissue	UBERON:0001134	38.16	gold quality
monocyte	CL:0000576	37.44	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
leukocyte	CL:0000738	36.55	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.28	gold quality
muscle tissue	UBERON:0002385	34.60	gold quality
calcaneal tendon	UBERON:0003701	34.22	gold quality
right lung	UBERON:0002167	33.01	gold quality
upper lobe of left lung	UBERON:0008952	32.20	silver quality
lung	UBERON:0002048	32.13	silver quality
bone marrow	UBERON:0002371	32.00	gold quality
prefrontal cortex	UBERON:0000451	30.55	gold quality
cortex of kidney	UBERON:0001225	30.30	gold quality
primary visual cortex	UBERON:0002436	29.95	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
lymph node	UBERON:0000029	29.85	gold quality
liver	UBERON:0002107	29.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting C18orf63, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3529-3P	99.90	73.55	3045

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm17266	ENSMUSG00000117781
rattus_norvegicus	C18h18orf63	ENSRNOG00000038241
caenorhabditis_elegans	F21F3.4	WBGENE00017674

Protein

Protein identifiers

Uncharacterized protein C18orf63 — Q68DL7 (reviewed: Q68DL7)

All UniProt accessions (1): Q68DL7

RefSeq proteins (1): NP_001167594* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031643	DUF4708	Domain

Pfam: PF15813

UniProt features (7 total): region of interest 2, compositionally biased region 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68DL7-F1	62.31	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, chr18q22, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MALE_SEX_DIFFERENTIATION, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, MIR3662, MIR1277_5P, MIR548E_5P, LET_7A_3P, MIR98_3P, LET_7F_1_3P, LET_7B_3P, MIR7_1_3P, MIR7_2_3P

GO Biological Process (1): male gonad development (GO:0008584)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gonad development	1
development of primary male sexual characteristics	1

Protein interactions and networks

STRING

72 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C18orf63	LRGUK	Q96M69	507
C18orf63	SLFN12L	Q6IEE8	507
C18orf63	AGBL3	Q8NEM8	436
C18orf63	CHCHD3	Q9NX63	375
C18orf63	ZNF236	Q9UL36	266
C18orf63	ENPP5	Q9UJA9	224
C18orf63	CDHR5	Q9HBB8	224
C18orf63	WDFY1	Q8IWB7	223
C18orf63	MEP1B	Q16820	223
C18orf63	AKR7A3	O95154	223
C18orf63	SLC14A2	Q15849	222
C18orf63	TM4SF4	P48230	213
C18orf63	CNDP1	Q96KN2	192
C18orf63	TNP1	P09430	181
C18orf63	CDH16	O75309	177

IntAct

7 interactions, top by confidence:

A	B	Type	Score
JUN		psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (10): C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS), RPS6KC1 (Cross-Linking-MS (XL-MS)), C18orf63 (Affinity Capture-MS), C18orf63 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, A7MBJ2, B1WC58, B2RYR0, B4F7C4, D2H3M0, D3ZF42, E1BPH3, E2QTD3, O35618, O60934, P61590, P61591, P61592, P61593, P61594, Q17RS7, Q28FY7, Q561R3, Q5IFK1, Q5PQK4, Q5RCV3, Q5SU73, Q5U5Q9, Q5VCS6, Q5XIN1, Q68DL7, Q6P2K3, Q6P7W0, Q6PDH4, Q6ZVT6, Q7TP65, Q7TT79, Q7ZZH7, Q86VV4, Q8BMI4, Q8BUH8, Q8IW35, Q8IYW5, Q8NAT2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1340168	GRCh37/hg19 18q22.2-23(chr18:68585785-74978794)x1	Pathogenic
1526624	GRCh37/hg19 18q21.2-23(chr18:53100584-78014123)	Pathogenic
816043	GRCh37/hg19 18q22.1-23(chr18:66620343-74065460)x1	Pathogenic
816044	GRCh37/hg19 18q22.1-23(chr18:61994711-74293556)x1	Pathogenic

SpliceAI

1966 predictions. Top by Δscore:

Variant	Effect	Δscore
18:74316073:G:GT	donor_gain	1.0000
18:74316106:GTTT:G	donor_gain	1.0000
18:74320592:G:GC	donor_loss	1.0000
18:74320592:G:GG	donor_gain	1.0000
18:74320593:T:A	donor_loss	1.0000
18:74320594:TAG:T	donor_loss	1.0000
18:74320595:AG:A	donor_loss	1.0000
18:74322691:GTTAC:G	acceptor_loss	1.0000
18:74322692:TTACA:T	acceptor_loss	1.0000
18:74322693:TACA:T	acceptor_loss	1.0000
18:74322694:ACAG:A	acceptor_loss	1.0000
18:74322695:CA:C	acceptor_loss	1.0000
18:74322696:AG:A	acceptor_loss	1.0000
18:74342030:A:AG	acceptor_gain	1.0000
18:74342031:G:GG	acceptor_gain	1.0000
18:74316089:G:GT	donor_gain	0.9900
18:74316110:G:GG	donor_gain	0.9900
18:74316208:G:GT	donor_gain	0.9900
18:74317050:A:AG	donor_gain	0.9900
18:74317051:G:GG	donor_gain	0.9900
18:74317095:G:GG	donor_gain	0.9900
18:74320507:CCACA:C	acceptor_loss	0.9900
18:74320508:CACAG:C	acceptor_loss	0.9900
18:74320509:ACAGG:A	acceptor_loss	0.9900
18:74320510:CAGGC:C	acceptor_loss	0.9900
18:74320511:A:AG	acceptor_gain	0.9900
18:74320511:A:G	acceptor_loss	0.9900
18:74320512:G:GG	acceptor_gain	0.9900
18:74320512:GGCA:G	acceptor_gain	0.9900
18:74320581:T:TA	donor_gain	0.9900

AlphaMissense

4550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:74328028:T:A	W118R	0.991
18:74328028:T:C	W118R	0.991
18:74329031:C:A	A140D	0.986
18:74329034:T:A	V141D	0.981
18:74329030:G:C	A140P	0.979
18:74328030:G:C	W118C	0.978
18:74328030:G:T	W118C	0.978
18:74342298:T:C	F256L	0.978
18:74342300:C:A	F256L	0.978
18:74342300:C:G	F256L	0.978
18:74342117:T:A	W233R	0.977
18:74342117:T:C	W233R	0.977
18:74338815:T:A	V201D	0.976
18:74327989:T:C	C105R	0.974
18:74330902:T:C	L154P	0.974
18:74327991:C:G	C105W	0.973
18:74338754:T:C	F181L	0.973
18:74338756:T:A	F181L	0.973
18:74338756:T:G	F181L	0.973
18:74338810:C:G	C199W	0.973
18:74327981:T:C	L102P	0.970
18:74329003:T:C	F131L	0.969
18:74329005:T:A	F131L	0.969
18:74329005:T:G	F131L	0.969
18:74338808:T:C	C199R	0.969
18:74343631:T:C	C303R	0.969
18:74320542:T:C	L55P	0.968
18:74327993:T:C	L106P	0.968
18:74338755:T:C	F181S	0.967
18:74342119:G:C	W233C	0.966

dbSNP variants (sampled 300 via entrez): RS1000056148 (18:74342494 A>C,G), RS1000086806 (18:74341936 G>A,T), RS1000141760 (18:74356489 A>G), RS1000270555 (18:74349946 A>G), RS1000315581 (18:74334737 C>T), RS1000343997 (18:74355995 G>A,T), RS1000345649 (18:74336670 T>C), RS1000371999 (18:74355758 A>G), RS1000376724 (18:74336317 A>G,T), RS1000504711 (18:74347849 C>A,G,T), RS1000513788 (18:74344725 A>G), RS1000676251 (18:74354569 A>G), RS1000708395 (18:74354219 A>G), RS1000713317 (18:74337865 A>C), RS1000718515 (18:74338082 T>C)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067191 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tebuconazole	increases expression	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651011	Binding	Binding affinity to human C18orf63 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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