C9orf40

Summary

C9orf40 (chromosome 9 open reading frame 40, HGNC:23433) is a protein-coding gene on chromosome 9q21.13, encoding Uncharacterized protein C9orf40 (Q8IXQ3).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 9 total — 2 pathogenic
• MANE Select transcript: NM_017998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23433
Approved symbol	C9orf40
Name	chromosome 9 open reading frame 40
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10110
Ensembl gene	ENSG00000135045
Ensembl biotype	protein_coding
Entrez	55071

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376854

RefSeq mRNA: 1 — MANE Select: NM_017998 NM_017998

CCDS: CCDS6648

Canonical transcript exons

ENST00000376854 — 2 exons

Exon	Start	End
ENSE00001471935	74946583	74948206
ENSE00001471939	74952186	74952912

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2607 / max 82.8317, expressed in 1737 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101021	8.6654	1682
101022	2.5952	1321

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.59	gold quality
oocyte	CL:0000023	89.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.24	gold quality
jejunal mucosa	UBERON:0000399	86.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.89	silver quality
vena cava	UBERON:0004087	85.50	silver quality
pericardium	UBERON:0002407	85.33	gold quality
mucosa of transverse colon	UBERON:0004991	84.72	gold quality
cardia of stomach	UBERON:0001162	84.59	gold quality
trabecular bone tissue	UBERON:0002483	84.57	gold quality
pons	UBERON:0000988	84.23	gold quality
jejunum	UBERON:0002115	83.81	gold quality
superior surface of tongue	UBERON:0007371	82.92	gold quality
saphenous vein	UBERON:0007318	82.85	gold quality
ventral tegmental area	UBERON:0002691	82.69	gold quality
subthalamic nucleus	UBERON:0001906	82.31	gold quality
pharyngeal mucosa	UBERON:0000355	82.13	gold quality
colonic mucosa	UBERON:0000317	81.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.36	gold quality
inferior vagus X ganglion	UBERON:0005363	81.03	gold quality
body of tongue	UBERON:0011876	80.61	silver quality
superior vestibular nucleus	UBERON:0007227	80.50	gold quality
duodenum	UBERON:0002114	80.39	gold quality
cortical plate	UBERON:0005343	80.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.34	gold quality
substantia nigra pars reticulata	UBERON:0001966	80.27	silver quality
tongue	UBERON:0001723	80.25	silver quality
ventricular zone	UBERON:0003053	80.01	gold quality
pylorus	UBERON:0001166	79.73	gold quality
nipple	UBERON:0002030	79.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.41
E-MTAB-7381	no	50.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting C9orf40, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
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-5696	99.98	72.36	4487
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	D030056L22Rik	ENSMUSG00000047044
rattus_norvegicus	C1h9orf40	ENSRNOG00000025644

Protein

Protein identifiers

Uncharacterized protein C9orf40 — Q8IXQ3 (reviewed: Q8IXQ3)

All UniProt accessions (1): Q8IXQ3

RefSeq proteins (1): NP_060468* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033461	WRNPLPNID	Domain
IPR042349	C9orf40-like	Family

Pfam: PF15017

UniProt features (8 total): compositionally biased region 3, modified residue 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXQ3-F1	60.37	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 69, 76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, CTATGCA_MIR153, WEI_MYCN_TARGETS_WITH_E_BOX, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, FISCHER_DREAM_TARGETS, RASHI_RESPONSE_TO_IONIZING_RADIATION_6, BERENJENO_TRANSFORMED_BY_RHOA_UP, SENESE_HDAC3_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, YGCGYRCGC_UNKNOWN, SCGGAAGY_ELK1_02, chr9q21, MGGAAGTG_GABP_B, CHICAS_RB1_TARGETS_SENESCENT, JOHNSTONE_PARVB_TARGETS_3_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C9orf40	J3KS56	J3KS56	595
C9orf40	CCDC150	Q8NCX0	556
C9orf40	HAUS4	Q9H6D7	506
C9orf40	CEP15	Q9HBI5	506
C9orf40	ANKRD62	A6NC57	447
C9orf40	CT62	P0C5K7	447
C9orf40	GTF3C4	Q9UKN8	434
C9orf40	DONSON	Q9NYP3	426
C9orf40	FAM174A	Q8TBP5	398
C9orf40	MGME1	Q9BQP7	386
C9orf40	CDCA4	Q9BXL8	374
C9orf40	ENTREP2	O60320	371
C9orf40	ZSWIM3	Q96MP5	370
C9orf40	NMRK1	Q9NWW6	370
C9orf40	ELOA	Q14241	366

IntAct

20 interactions, top by confidence:

A	B	Type	Score
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
DNAJB8	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.530
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
RNF152	C9orf40	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PLOD1	COL25A1	psi-mi:“MI:0914”(association)	0.350
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.350
PLPPR2	SEC24D	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
C9orf40	KPNA4	psi-mi:“MI:0914”(association)	0.350
PLOD1	PLK4	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
C9orf40	TRAPPC3	psi-mi:“MI:0914”(association)	0.350
SLC15A1	MEN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): C9orf40 (Affinity Capture-RNA), C9orf40 (Affinity Capture-RNA), C9orf40 (Affinity Capture-RNA), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS)

ESM2 similar proteins: A0A2Z4LIS9, A6NEQ2, A6NJT0, A7MB34, G3UXB3, O15370, O35182, O43541, O70218, O70220, O75474, O89113, P09066, P0C1Z6, P12980, P17542, P19622, P22091, P78367, P82976, P97503, Q04890, Q05916, Q05917, Q10586, Q15270, Q17QH7, Q32PF6, Q5TGY3, Q5VY09, Q60925, Q66H24, Q6NZ36, Q6PAN7, Q7RTU5, Q80VF6, Q8IXQ3, Q8K025, Q8VCE4, Q8WY41

Diamond homologs: Q66H24, Q8IXQ3, Q8VCE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4682740	GRCh37/hg19 9q21.13-21.2(chr9:77109597-80718096)x1	Pathogenic
59109	GRCh38/hg38 9q21.13-21.31(chr9:73706686-80370629)x1	Pathogenic

SpliceAI

351 predictions. Top by Δscore:

Variant	Effect	Δscore
9:74948209:T:C	acceptor_gain	1.0000
9:74948202:TTGTG:T	acceptor_gain	0.9900
9:74948203:TGTG:T	acceptor_gain	0.9900
9:74948204:G:C	acceptor_gain	0.9900
9:74948204:G:GC	acceptor_gain	0.9900
9:74948205:TG:T	acceptor_gain	0.9900
9:74948207:C:CC	acceptor_gain	0.9900
9:74948207:C:T	acceptor_loss	0.9900
9:74948208:T:C	acceptor_gain	0.9900
9:74948209:T:TC	acceptor_gain	0.9900
9:74952351:ACGCT:A	donor_gain	0.9900
9:74952352:CG:C	donor_gain	0.9900
9:74952352:CGCTC:C	donor_gain	0.9900
9:74952355:T:A	donor_gain	0.9900
9:74948200:CATTG:C	acceptor_gain	0.9800
9:74948206:GCTTT:G	acceptor_gain	0.9800
9:74948208:T:TC	acceptor_gain	0.9800
9:74948203:TGTGC:T	acceptor_gain	0.9700
9:74948204:GTGCT:G	acceptor_gain	0.9700
9:74948205:TGCTT:T	acceptor_gain	0.9700
9:74948207:CTTTA:C	acceptor_gain	0.9700
9:74952327:G:A	donor_gain	0.9700
9:74952352:CGCT:C	donor_gain	0.9700
9:74948208:T:A	acceptor_gain	0.9500
9:74951849:ATGC:A	donor_gain	0.9500
9:74952346:T:TA	donor_gain	0.9500
9:74951910:C:A	donor_gain	0.9300
9:74951658:TTG:T	donor_gain	0.9100
9:74952351:A:AC	donor_gain	0.9100
9:74952352:C:CC	donor_gain	0.9100

AlphaMissense

1253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:74948165:C:A	W156C	0.997
9:74948165:C:G	W156C	0.997
9:74948167:A:G	W156R	0.997
9:74948167:A:T	W156R	0.997
9:74948174:G:C	F153L	0.997
9:74948174:G:T	F153L	0.997
9:74948176:A:G	F153L	0.997
9:74948162:C:A	R157S	0.994
9:74948162:C:G	R157S	0.994
9:74948175:A:G	F153S	0.994
9:74948180:A:C	N151K	0.992
9:74948180:A:T	N151K	0.992
9:74948163:C:G	R157T	0.991
9:74948163:C:A	R157M	0.990
9:74948166:C:G	W156S	0.989
9:74948175:A:C	F153C	0.989
9:74948154:A:G	L160S	0.988
9:74948170:A:C	Y155D	0.988
9:74948185:A:G	Y150H	0.987
9:74948170:A:G	Y155H	0.986
9:74948184:T:G	Y150S	0.986
9:74948185:A:C	Y150D	0.986
9:74952576:G:C	F12L	0.986
9:74952576:G:T	F12L	0.986
9:74952578:A:G	F12L	0.986
9:74952603:C:A	K3N	0.986
9:74952603:C:G	K3N	0.986
9:74948192:A:C	F147L	0.984
9:74948192:A:T	F147L	0.984
9:74948194:A:G	F147L	0.984

dbSNP variants (sampled 300 via entrez): RS1000047801 (9:74952848 C>G), RS1000099920 (9:74952683 C>A), RS1002242402 (9:74946483 CTAA>C), RS1002422565 (9:74953071 C>A), RS1002424706 (9:74953282 C>A,T), RS1002567608 (9:74946953 A>G), RS1002685387 (9:74946761 A>G,T), RS1003051157 (9:74950197 C>A,T), RS1003082463 (9:74950561 A>C), RS1003379044 (9:74951817 C>T), RS1003664821 (9:74950305 G>A,T), RS1003718573 (9:74950011 G>A), RS1004570086 (9:74949975 C>A,G), RS1004887366 (9:74949678 T>C), RS1005561945 (9:74946665 A>G)

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

3 associations (top):

Study	Trait	p-value
GCST005124_2	Urinary magnesium-to-creatinine ratio	4.000000e-13
GCST006923_14	Loneliness	5.000000e-09
GCST006924_6	Loneliness (MTAG)	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008449	magnesium:creatinine ratio measurement
EFO:0007865	loneliness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
Valproic Acid	increases expression, affects expression	4
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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