C12orf56

Summary

C12orf56 (chromosome 12 open reading frame 56, HGNC:26967) is a protein-coding gene on chromosome 12q14.2, encoding Uncharacterized protein C12orf56 (Q8IXR9).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total — 1 pathogenic
• MANE Select transcript: NM_001170633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26967
Approved symbol	C12orf56
Name	chromosome 12 open reading frame 56
Location	12q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185306
Ensembl biotype	protein_coding
Entrez	115749

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000333722, ENST00000535515, ENST00000536975, ENST00000541802, ENST00000542397, ENST00000543259, ENST00000543942, ENST00000924490

RefSeq mRNA: 2 — MANE Select: NM_001170633 NM_001099676, NM_001170633

CCDS: CCDS44935, CCDS61182

Canonical transcript exons

ENST00000543942 — 13 exons

Exon	Start	End
ENSE00001318510	64352894	64353056
ENSE00001323040	64330960	64331032
ENSE00002219632	64318575	64318980
ENSE00002223110	64264762	64267288
ENSE00003506888	64270536	64270714
ENSE00003516087	64312679	64312752
ENSE00003527518	64277680	64277803
ENSE00003535156	64390314	64390758
ENSE00003555378	64285954	64286060
ENSE00003556518	64274901	64274975
ENSE00003607020	64303635	64303779
ENSE00003656535	64284664	64284753
ENSE00003671482	64275298	64275372

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 86.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1703 / max 19.3855, expressed in 64 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131852	0.0749	29
131853	0.0583	17
131851	0.0371	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	86.23	gold quality
lower esophagus mucosa	UBERON:0035834	84.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.89	gold quality
sural nerve	UBERON:0015488	78.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.43	silver quality
tibial nerve	UBERON:0001323	76.39	gold quality
esophagus squamous epithelium	UBERON:0006920	73.70	silver quality
left testis	UBERON:0004533	73.47	gold quality
esophagus mucosa	UBERON:0002469	72.88	gold quality
testis	UBERON:0000473	72.49	gold quality
right testis	UBERON:0004534	71.22	gold quality
gingival epithelium	UBERON:0001949	70.15	silver quality
kidney epithelium	UBERON:0004819	66.13	gold quality
vagina	UBERON:0000996	65.04	gold quality
placenta	UBERON:0001987	63.91	gold quality
skin of abdomen	UBERON:0001416	63.69	gold quality
skin of leg	UBERON:0001511	63.68	gold quality
corpus callosum	UBERON:0002336	63.54	gold quality
adult mammalian kidney	UBERON:0000082	63.49	gold quality
pancreatic ductal cell	CL:0002079	62.72	silver quality
mucosa of transverse colon	UBERON:0004991	62.31	gold quality
upper leg skin	UBERON:0004262	61.99	gold quality
tibialis anterior	UBERON:0001385	61.95	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	61.62	gold quality
zone of skin	UBERON:0000014	61.50	gold quality
ileal mucosa	UBERON:0000331	60.48	silver quality
amniotic fluid	UBERON:0000173	59.53	gold quality
oral cavity	UBERON:0000167	58.56	silver quality
kidney	UBERON:0002113	57.32	gold quality
metanephros cortex	UBERON:0010533	57.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting C12orf56, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-5681B	94.82	69.30	514

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-258f14.2	ENSDARG00000073963
mus_musculus	D930020B18Rik	ENSMUSG00000047642
rattus_norvegicus	C7h12orf56	ENSRNOG00000023824

Protein

Protein identifiers

Uncharacterized protein C12orf56 — Q8IXR9 (reviewed: Q8IXR9)

All UniProt accessions (2): Q8IXR9, H0YGI1

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXR9-1	1	yes
Q8IXR9-2	2

RefSeq proteins (2): NP_001093146, NP_001164104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027878	DUF4551	Family

Pfam: PF15087

UniProt features (4 total): chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXR9-F1	71.54	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): NIKOLSKY_BREAST_CANCER_12Q13_Q21_AMPLICON, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, CIITA_TARGET_GENES, MIR7_1_3P, MIR7_2_3P, MIR551B_5P, MIR3143, MIR6758_5P, MIR6856_5P, MIR10395_5P, GSE14308_TH2_VS_INDUCED_TREG_DN, GSE14308_TH1_VS_INDUCED_TREG_DN, GSE14308_TH1_VS_NATURAL_TREG_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C12orf56	C11orf16	Q9NQ32	623
C12orf56	C3orf22	Q8N5N4	620
C12orf56	RNASE12	Q5GAN4	582
C12orf56	SMIM17	P0DL12	577
C12orf56	SH2D7	A6NKC9	571
C12orf56	C22orf42	Q6IC83	544
C12orf56	CC2D2B	Q6DHV5	544
C12orf56	C1orf167	Q5SNV9	544
C12orf56	ANKRD62	A6NC57	543
C12orf56	SPDYE4	A6NLX3	527
C12orf56	CLPSL1	A2RUU4	512
C12orf56	EPCIP	Q9NYP8	507
C12orf56	RD3L	P0DJH9	507
C12orf56	SMIM21	Q3B7S5	507
C12orf56	MGAT4D	A6NG13	505

IntAct

0 interactions, top by confidence:

BioGRID (2): C12orf56 (Synthetic Lethality), C12orf56 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L4, A1A5R8, A2RRS8, A5PLL1, B0BF33, D4A039, D4AEC2, P0C6C1, Q08AD1, Q08AX9, Q0P557, Q0VA42, Q12923, Q13009, Q3B7T8, Q3UMB5, Q3UMG5, Q3UQI9, Q3UUF8, Q4R9E9, Q5JTW2, Q5PQ89, Q5SUS0, Q5TB30, Q5VUJ6, Q5ZIX8, Q64512, Q68FF0, Q6AY22, Q6GQJ2, Q6IE81, Q6IE82, Q6ING4, Q6IRU7, Q6NPP4, Q6NSI8, Q6P1H6, Q6ZPI0, Q7TP65, Q7ZVP1

Diamond homologs: Q4R9E9, Q8CCC3, Q8IXR9

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	1
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3244245	NC_000012.11:g.(?64173741)(68052493_?)del	Pathogenic

SpliceAI

2073 predictions. Top by Δscore:

Variant	Effect	Δscore
12:64274899:A:AC	donor_gain	1.0000
12:64274900:C:CC	donor_gain	1.0000
12:64284662:A:AC	donor_gain	1.0000
12:64284663:C:CC	donor_gain	1.0000
12:64284663:CTT:C	donor_gain	1.0000
12:64284670:G:C	donor_gain	1.0000
12:64303630:CTTA:C	donor_loss	1.0000
12:64303631:TTAC:T	donor_loss	1.0000
12:64303632:TACCT:T	donor_loss	1.0000
12:64303633:A:AC	donor_gain	1.0000
12:64303633:AC:A	donor_gain	1.0000
12:64303633:ACCTT:A	donor_gain	1.0000
12:64303634:C:CC	donor_gain	1.0000
12:64303634:CC:C	donor_gain	1.0000
12:64303634:CCT:C	donor_gain	1.0000
12:64303634:CCTT:C	donor_gain	1.0000
12:64303634:CCTTC:C	donor_gain	1.0000
12:64303775:CAGAC:C	acceptor_gain	1.0000
12:64303780:C:CA	acceptor_loss	1.0000
12:64303781:T:G	acceptor_loss	1.0000
12:64312749:CTTT:C	acceptor_gain	1.0000
12:64312750:TTT:T	acceptor_gain	1.0000
12:64312750:TTTC:T	acceptor_loss	1.0000
12:64312751:TT:T	acceptor_gain	1.0000
12:64312752:TCT:T	acceptor_loss	1.0000
12:64312753:C:CA	acceptor_loss	1.0000
12:64312753:C:CC	acceptor_gain	1.0000
12:64331033:C:CC	acceptor_gain	1.0000
12:64331034:T:C	acceptor_gain	1.0000
12:64331034:T:TC	acceptor_gain	1.0000

AlphaMissense

4087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:64303640:A:G	W370R	0.992
12:64303640:A:T	W370R	0.992
12:64390506:G:C	F20L	0.981
12:64390506:G:T	F20L	0.981
12:64390508:A:G	F20L	0.981
12:64303684:A:G	L355P	0.980
12:64303747:A:G	L334P	0.977
12:64390398:G:C	S56R	0.977
12:64390398:G:T	S56R	0.977
12:64390400:T:G	S56R	0.977
12:64353036:A:C	F91L	0.974
12:64353036:A:T	F91L	0.974
12:64353038:A:G	F91L	0.974
12:64303641:G:C	F369L	0.972
12:64303641:G:T	F369L	0.972
12:64303643:A:G	F369L	0.972
12:64318648:A:G	L274P	0.972
12:64390381:A:G	L62P	0.971
12:64303650:T:A	K366N	0.970
12:64303650:T:G	K366N	0.970
12:64303638:C:A	W370C	0.969
12:64303638:C:G	W370C	0.969
12:64390405:A:T	V54E	0.969
12:64390451:A:G	C39R	0.966
12:64390504:A:G	L21P	0.966
12:64303642:A:G	F369S	0.965
12:64390387:A:T	V60D	0.962
12:64318592:A:G	W293R	0.961
12:64318592:A:T	W293R	0.961
12:64285957:A:G	L406P	0.960

dbSNP variants (sampled 300 via entrez): RS1000012059 (12:64378779 G>A,C), RS1000016324 (12:64391957 C>T), RS1000019138 (12:64279603 T>G), RS1000029027 (12:64381981 G>T), RS1000071283 (12:64279967 C>A,G), RS1000075147 (12:64330097 G>A), RS1000095539 (12:64338924 A>G), RS1000145069 (12:64338194 GC>G), RS1000162046 (12:64324529 C>T), RS1000174246 (12:64371658 C>A,T), RS1000189819 (12:64385474 A>C,G), RS1000201017 (12:64328032 TATAATA>T,TATA), RS1000232731 (12:64379172 T>C), RS1000271192 (12:64286568 A>G), RS1000293204 (12:64266223 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:618908, MIM:252940

GenCC curated gene-disease

Mondo (2): Silver-Russell syndrome 5 (MONDO:0020795), mucopolysaccharidosis type 3D (MONDO:0009658)

Orphanet (2): Mucopolysaccharidosis type 3 (Orphanet:581), Sanfilippo syndrome type D (Orphanet:79272)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020029_461	Waist circumference adjusted for body mass index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
bisphenol A	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases 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
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05648851	Not specified	COMPLETED	A Natural History Study of Sanfilippo Syndrome Type D