C6orf89

Summary

C6orf89 (chromosome 6 open reading frame 89, HGNC:21114) is a protein-coding gene on chromosome 6p21.2, encoding Bombesin receptor-activated protein C6orf89 (Q6UWU4). Exhibits histone deacetylase (HDAC) enhancer properties.

Involved in several processes, including chromatin remodeling; epithelial cell proliferation; and wound healing. Located in several cellular components, including Golgi membrane; midbody; and nucleolus.

Source: NCBI Gene 221477 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 29 total — 2 likely-pathogenic
• MANE Select transcript: NM_001286635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21114
Approved symbol	C6orf89
Name	chromosome 6 open reading frame 89
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25357, BRAP
Ensembl gene	ENSG00000198663
Ensembl biotype	protein_coding
OMIM	616642
Entrez	221477

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 27 protein_coding

ENST00000355190, ENST00000359359, ENST00000373685, ENST00000480824, ENST00000909351, ENST00000909352, ENST00000909353, ENST00000909354, ENST00000909355, ENST00000909356, ENST00000909357, ENST00000909358, ENST00000909359, ENST00000909360, ENST00000909361, ENST00000920027, ENST00000920028, ENST00000920029, ENST00000920030, ENST00000946073, ENST00000946074, ENST00000946075, ENST00000946076, ENST00000946077, ENST00000946078, ENST00000946079, ENST00000946080

RefSeq mRNA: 4 — MANE Select: NM_001286635 NM_001286635, NM_001286636, NM_001286637, NM_152734

CCDS: CCDS4827, CCDS69100, CCDS75444

Canonical transcript exons

ENST00000480824 — 9 exons

Exon	Start	End
ENSE00001085210	36916445	36916574
ENSE00001272611	36919578	36919701
ENSE00001708379	36894504	36894603
ENSE00001894872	36885952	36886028
ENSE00003694742	36899426	36899633
ENSE00003695977	36902221	36902434
ENSE00003699792	36923347	36928964
ENSE00003700280	36914554	36914693
ENSE00003701709	36914284	36914435

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.2197 / max 407.0797, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67572	51.5527	1823
67570	2.1828	1147
67571	1.4456	977
67569	0.0308	3
67568	0.0078	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	96.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.49	gold quality
islet of Langerhans	UBERON:0000006	96.23	gold quality
kidney epithelium	UBERON:0004819	95.59	gold quality
tendon of biceps brachii	UBERON:0008188	95.36	gold quality
smooth muscle tissue	UBERON:0001135	94.76	gold quality
corpus epididymis	UBERON:0004359	94.62	gold quality
stromal cell of endometrium	CL:0002255	94.51	gold quality
myocardium	UBERON:0002349	93.93	gold quality
medial globus pallidus	UBERON:0002477	93.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.73	gold quality
nipple	UBERON:0002030	93.50	gold quality
globus pallidus	UBERON:0001875	93.47	gold quality
urethra	UBERON:0000057	93.24	gold quality
tibialis anterior	UBERON:0001385	93.19	silver quality
sperm	CL:0000019	93.00	gold quality
gall bladder	UBERON:0002110	93.00	gold quality
upper arm skin	UBERON:0004263	92.88	gold quality
rectum	UBERON:0001052	92.78	gold quality
postcentral gyrus	UBERON:0002581	92.76	gold quality
inferior vagus X ganglion	UBERON:0005363	92.69	gold quality
right testis	UBERON:0004534	92.60	gold quality
pancreas	UBERON:0001264	92.56	gold quality
lateral globus pallidus	UBERON:0002476	92.56	gold quality
parietal lobe	UBERON:0001872	92.51	gold quality
heart left ventricle	UBERON:0002084	92.51	gold quality
cardiac ventricle	UBERON:0002082	92.49	gold quality
substantia nigra pars compacta	UBERON:0001965	92.47	gold quality
nasal cavity epithelium	UBERON:0005384	92.43	gold quality
layer of synovial tissue	UBERON:0007616	92.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.72
E-ENAD-17	no	2211.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

176 targeting C6orf89, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
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-548N	99.98	71.94	4170
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893

Literature-anchored findings (GeneRIF, showing 6)

• Data show that BRAP locates in the membrane and cytoplasm, suggesting that this protein is a cytoplasm protein, which promotes cell cycle and wound repair of HBECs. (PMID:21857995)
• Overexpression of BRAP may play a role during the antigen presenting process of bronchial epithelium by inhibiting the antigen uptake ability of bronchial epithelial cells. (PMID:22930588)
• C60rf89 is a gene that encodes three distinct proteins with the capacity to enhance the activity of histone deacetylases (HDACs) in the nucleolus, the Golgi and the midbody (PMID:23460338)
• C6orf89 encodes one soluble and two type II membrane proteins that function as histone deacetylase enhancers. The 34sp is selectively targeted to the nucleolus and is retained in nucleolar organizer regions in mitotic cells. The 34sp is integrated into the ribosomal gene transcription machinery and is relocalized to the nucleolus upon the arrest of rDNA transcription, protein synthesis, and PI3K/mTORC signalling. (PMID:23460338)
• Data indicate that bombesin receptor-activated protein (BRAP) might increase histone deacetylases 1/2 (HDAC) activity that leads to NF-kappa B (NF-kappaB) activation via its putative C-terminal domain. (PMID:26460487)
• results suggest BRAP plays an important role in airway inflammation and its overexpression may regulate NE-induced MUC5AC hypersecretion in HBE16 cells via the EGFR/ERK/NF-kappaB signaling pathway (PMID:28476309)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:162255	ENSDARG00000078301
mus_musculus	BC004004	ENSMUSG00000052712
rattus_norvegicus	C20h6orf89	ENSRNOG00000000524

Protein

Protein identifiers

Bombesin receptor-activated protein C6orf89 — Q6UWU4 (reviewed: Q6UWU4)

Alternative names: Amfion

All UniProt accessions (1): Q6UWU4

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits histone deacetylase (HDAC) enhancer properties. May play a role in cell cycle progression and wound repair of bronchial epithelial cells.

Subunit / interactions. Homodimer. Interacts with BRS3. Interacts (via N-terminus) with SIN3B.

Subcellular location. Golgi apparatus membrane. Midbody Golgi apparatus membrane. Midbody Cytoplasm. Nucleus. Nucleolus.

Post-translational modifications. Glycosylated.

Miscellaneous. Named amfion, after ’the 4 Amfion heroes in Greek mythology and their deeds in different locations within the mother land.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6UWU4-1	1, 42/116mp	yes
Q6UWU4-2	2
Q6UWU4-3	3, 34/64sp

RefSeq proteins (4): NP_001273564, NP_001273565, NP_001273566, NP_689947 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038757	BRAP	Family

UniProt features (10 total): sequence conflict 4, topological domain 2, splice variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWU4-F1	72.24	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 279 (showing top): TSUNODA_CISPLATIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_255, MODULE_317, AP2_Q3, GOLDRATH_ANTIGEN_RESPONSE, GOBP_WOUND_HEALING, UEDA_PERIFERAL_CLOCK, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (9): chromatin remodeling (GO:0006338), autophagy (GO:0006914), collagen metabolic process (GO:0032963), wound healing (GO:0042060), positive regulation of cell cycle (GO:0045787), fibroblast proliferation (GO:0048144), epithelial cell proliferation (GO:0050673), connective tissue replacement (GO:0097709), response to bleomycin (GO:1904975)

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

GO Cellular Component (8): Golgi membrane (GO:0000139), nucleolus (GO:0005730), cytoplasm (GO:0005737), plasma membrane (GO:0005886), midbody (GO:0030496), nucleus (GO:0005634), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell population proliferation	2
intracellular membrane-bounded organelle	2
chromatin organization	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
metabolic process	1
response to wounding	1
tissue regeneration	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
tissue remodeling	1
response to nitrogen compound	1
response to oxygen-containing compound	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C6orf89	BRS3	P32247	810
C6orf89	NOXRED1	Q6NXP6	436
C6orf89	KIAA1328	Q86T90	395
C6orf89	PRIM2	P49643	380
C6orf89	C1orf56	Q9BUN1	371
C6orf89	RBM46	Q8TBY0	336
C6orf89	ABCD4	O14678	325
C6orf89	C19orf33	Q9GZP8	323
C6orf89	SPATA20	Q8TB22	320
C6orf89	SAP30L	Q9HAJ7	306
C6orf89	KIZ	Q2M2Z5	299
C6orf89	KCNMB3	Q9NPA1	298
C6orf89	CHURC1	Q8WUH1	298
C6orf89	ALMS1	Q8TCU4	295
C6orf89	FNDC3B	Q53EP0	290

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CD79A	ODR4	psi-mi:“MI:0914”(association)	0.530
C6orf89	PTRHD1	psi-mi:“MI:0915”(physical association)	0.400
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
MOGS	SRPX2	psi-mi:“MI:0914”(association)	0.350
PRG3	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): PTRHD1 (Affinity Capture-MS), PTRHD1 (Affinity Capture-MS), C6orf89 (Affinity Capture-MS), C6orf89 (Affinity Capture-MS), C6orf89 (Two-hybrid), C6orf89 (Affinity Capture-RNA), C6orf89 (Affinity Capture-MS), PTRHD1 (Affinity Capture-MS), C6orf89 (Affinity Capture-RNA), C6orf89 (Proximity Label-MS), C6orf89 (Proximity Label-MS), C6orf89 (Proximity Label-MS), C6orf89 (Proximity Label-MS), C6orf89 (Proximity Label-MS), C6orf89 (Proximity Label-MS)

ESM2 similar proteins: A0JMQ9, A1ZAV1, A4QNX3, D3YWQ0, F1MAB7, F1QX91, F4JY12, O08653, O54788, O75426, O76075, P24380, P59438, P68328, P97499, Q2T9Z2, Q4G017, Q4R327, Q4VC12, Q5BIR3, Q5PQN2, Q5R7R7, Q5R9Q8, Q5SPX3, Q5TEA3, Q5TH69, Q5Y5T3, Q6P6G2, Q6S6V7, Q6UWU4, Q6XUX1, Q6XUX2, Q7TT23, Q80TM9, Q8BJ83, Q8IYP9, Q8K1M8, Q8R079, Q99973, Q99KU6

Diamond homologs: A4QNX3, Q5R9Q8, Q6P6G2, Q6UWU4, Q99KU6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	6
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
155452	GRCh38/hg38 6p21.2(chr6:36822889-37159699)x1	Likely pathogenic
4073533	NM_016059.5(PPIL1):c.41_42delinsG (p.Val14fs)	Likely pathogenic

SpliceAI

1472 predictions. Top by Δscore:

Variant	Effect	Δscore
6:36871870:ATG:A	acceptor_gain	1.0000
6:36871871:TG:T	acceptor_gain	1.0000
6:36871873:C:CC	acceptor_gain	1.0000
6:36874711:CCTCA:C	donor_loss	1.0000
6:36874712:CTCAC:C	donor_loss	1.0000
6:36874713:TCA:T	donor_loss	1.0000
6:36874714:CA:C	donor_loss	1.0000
6:36874715:ACC:A	donor_loss	1.0000
6:36874716:C:CT	donor_loss	1.0000
6:36874814:T:TA	donor_gain	1.0000
6:36886025:GCAT:G	donor_gain	1.0000
6:36886027:ATGT:A	donor_loss	1.0000
6:36886028:TG:T	donor_loss	1.0000
6:36886029:G:GG	donor_gain	1.0000
6:36898947:G:GG	donor_gain	1.0000
6:36899422:TCA:T	acceptor_loss	1.0000
6:36899423:CAGG:C	acceptor_loss	1.0000
6:36899424:A:AG	acceptor_gain	1.0000
6:36899424:A:C	acceptor_loss	1.0000
6:36899424:AG:A	acceptor_gain	1.0000
6:36899424:AGG:A	acceptor_gain	1.0000
6:36899425:G:GA	acceptor_loss	1.0000
6:36899425:G:GG	acceptor_gain	1.0000
6:36899425:GG:G	acceptor_gain	1.0000
6:36899425:GGG:G	acceptor_gain	1.0000
6:36899606:G:GG	donor_gain	1.0000
6:36899632:AG:A	donor_loss	1.0000
6:36899634:GTAA:G	donor_loss	1.0000
6:36902215:TTGTA:T	acceptor_loss	1.0000
6:36902216:TGTA:T	acceptor_loss	1.0000

AlphaMissense

2285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:36899533:T:C	M30T	0.997
6:36899556:T:C	F38L	0.997
6:36899558:T:A	F38L	0.997
6:36899558:T:G	F38L	0.997
6:36899569:T:C	L42P	0.995
6:36899557:T:C	F38S	0.994
6:36899485:T:A	L14H	0.992
6:36899518:G:A	G25D	0.992
6:36899485:T:C	L14P	0.990
6:36899497:T:A	V18D	0.987
6:36899572:T:C	L43P	0.987
6:36899557:T:G	F38C	0.984
6:36899517:G:T	G25C	0.983
6:36899517:G:C	G25R	0.982
6:36899534:G:A	M30I	0.981
6:36899534:G:C	M30I	0.981
6:36899534:G:T	M30I	0.981
6:36923412:T:C	C339R	0.981
6:36899510:A:C	R22S	0.980
6:36899510:A:T	R22S	0.980
6:36899518:G:T	G25V	0.979
6:36899560:T:A	I39N	0.978
6:36899506:T:A	V21E	0.977
6:36923369:G:C	W324C	0.976
6:36923369:G:T	W324C	0.976
6:36899469:A:C	S9R	0.974
6:36899471:C:A	S9R	0.974
6:36899471:C:G	S9R	0.974
6:36899485:T:G	L14R	0.974
6:36923412:T:A	C339S	0.974

dbSNP variants (sampled 300 via entrez): RS1000028008 (6:36919673 G>C), RS1000084206 (6:36926421 T>G), RS1000120339 (6:36882942 T>C,G), RS1000131512 (6:36926057 C>T), RS1000150054 (6:36924892 C>T), RS1000305957 (6:36910951 A>G), RS1000309178 (6:36919998 A>C), RS1000534570 (6:36904293 C>G,T), RS1000643224 (6:36909263 T>C), RS1000646457 (6:36921510 C>T), RS1000705308 (6:36878713 T>A), RS1000725928 (6:36921888 C>T), RS1000760226 (6:36871785 G>A,T), RS1000865915 (6:36928884 A>G), RS1000872749 (6:36921559 C>T)

Disease associations

OMIM: gene MIM:616642 | disease phenotypes: MIM:619301

GenCC curated gene-disease

Mondo (1): pontocerebellar hypoplasia, type 14 (MONDO:0030258)

Orphanet (1): Pontocerebellar hypoplasia type 14 (Orphanet:613274)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002481_11	Acne (severe)	2.000000e-06
GCST012299_8	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Valproic Acid	affects expression, increases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	increases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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