EMC9

Summary

EMC9 (ER membrane protein complex subunit 9, HGNC:20273) is a protein-coding gene on chromosome 14q12, encoding ER membrane protein complex subunit 9 (Q9Y3B6). Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins.

Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in cytoplasm. Part of EMC complex.

Source: NCBI Gene 51016 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_016049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20273
Approved symbol	EMC9
Name	ER membrane protein complex subunit 9
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	CGI-112
Ensembl gene	ENSG00000100908
Ensembl biotype	protein_coding
Entrez	51016

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000216799, ENST00000419198, ENST00000558045, ENST00000558200, ENST00000559101, ENST00000560403, ENST00000560600, ENST00000872607, ENST00000872608, ENST00000940001, ENST00000940002, ENST00000967220

RefSeq mRNA: 5 — MANE Select: NM_016049 NM_001346874, NM_001346875, NM_001346876, NM_001346877, NM_016049

CCDS: CCDS86377, CCDS9613

Canonical transcript exons

ENST00000216799 — 6 exons

Exon	Start	End
ENSE00000654238	24139545	24139614
ENSE00000889357	24138965	24139196
ENSE00000889358	24141107	24141316
ENSE00001032002	24141438	24141591
ENSE00003546687	24140889	24140965
ENSE00003587802	24139360	24139454

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 95.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3952 / max 246.9450, expressed in 1791 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142533	9.6439	1719
142531	2.1600	1251
142530	1.8552	745
142532	0.7361	479

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	95.10	gold quality
adenohypophysis	UBERON:0002196	94.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.17	gold quality
cerebellar hemisphere	UBERON:0002245	94.11	gold quality
cerebellum	UBERON:0002037	94.04	gold quality
cerebellar cortex	UBERON:0002129	94.04	gold quality
mucosa of transverse colon	UBERON:0004991	93.82	gold quality
ventricular zone	UBERON:0003053	93.09	gold quality
right adrenal gland	UBERON:0001233	92.85	gold quality
left adrenal gland cortex	UBERON:0035825	92.76	gold quality
left adrenal gland	UBERON:0001234	92.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.65	gold quality
right adrenal gland cortex	UBERON:0035827	92.55	gold quality
granulocyte	CL:0000094	92.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.41	gold quality
adrenal gland	UBERON:0002369	91.39	gold quality
right lobe of liver	UBERON:0001114	91.23	gold quality
spleen	UBERON:0002106	91.16	gold quality
gastrocnemius	UBERON:0001388	91.14	gold quality
muscle of leg	UBERON:0001383	90.89	gold quality
duodenum	UBERON:0002114	90.80	gold quality
prostate gland	UBERON:0002367	90.78	gold quality
skeletal muscle tissue	UBERON:0001134	90.57	gold quality
hypothalamus	UBERON:0001898	90.56	gold quality
brain	UBERON:0000955	90.42	gold quality
metanephros cortex	UBERON:0010533	90.42	gold quality
ganglionic eminence	UBERON:0004023	90.18	gold quality
popliteal artery	UBERON:0002250	90.11	gold quality
tibial artery	UBERON:0007610	90.10	gold quality
right frontal lobe	UBERON:0002810	89.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Circular RNA circ-FAM158A promotes retinoblastoma progression by regulating miR-138-5p/SLC7A5 axis. (PMID:34102206)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	emc9	ENSDARG00000034633
mus_musculus	Emc9	ENSMUSG00000022217
rattus_norvegicus	Emc9	ENSRNOG00000019162
drosophila_melanogaster	EMC8-9	FBGN0034791
caenorhabditis_elegans	F25H2.4	WBGENE00009118

Paralogs (1): EMC8 (ENSG00000131148)

Protein

Protein identifiers

ER membrane protein complex subunit 9 — Q9Y3B6 (reviewed: Q9Y3B6)

Alternative names: Protein FAM158A

All UniProt accessions (3): Q9Y3B6, H0YKG4, H0YNH6

UniProt curated annotations — full annotation on UniProt →

Function. Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.

Subunit / interactions. Component of the ER membrane protein complex (EMC). EMC8 and EMC9 are mutually exclusive subunits of the EMC complex.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the EMC8/EMC9 family.

RefSeq proteins (5): NP_001333803, NP_001333804, NP_001333805, NP_001333806, NP_057133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005366	EMC8/9	Family
IPR037518	MPN	Domain

Pfam: PF03665

UniProt features (21 total): strand 9, helix 7, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6Y4L	X-RAY DIFFRACTION	2.2
6Z3W	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3B6-F1	91.35	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, chr14q12, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, DOUGLAS_BMI1_TARGETS_UP, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, MODULE_207, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, NUYTTEN_EZH2_TARGETS_DN, LEIN_PONS_MARKERS

GO Biological Process (2): protein insertion into ER membrane by stop-transfer membrane-anchor sequence (GO:0045050), tail-anchored membrane protein insertion into ER membrane (GO:0071816)

GO Molecular Function (2): protein binding (GO:0005515), membrane insertase activity (GO:0032977)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), EMC complex (GO:0072546), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein insertion into ER membrane	2
cellular anatomical structure	2
binding	1
establishment of protein localization to membrane	1
protein carrier activity	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMC9	EMC4	Q5J8M3	792
EMC9	EMC6	Q9BV81	792
EMC9	EMC3	Q9P0I2	774
EMC9	EMC7	Q9NPA0	747
EMC9	EMC2	Q15006	742
EMC9	MMGT1	Q8N4V1	736
EMC9	EMC1	Q8N766	736
EMC9	EMC10	Q5UCC4	689
EMC9	SOAT1	P35610	453
EMC9	ODF2L	Q9ULJ1	402
EMC9	ZNF528	Q3MIS6	357
EMC9	FDFT1	P37268	341
EMC9	ZC2HC1A	Q96GY0	325
EMC9	DBF4B	Q8NFT6	323
EMC9	UBAC2	Q8NBM4	284

IntAct

39 interactions, top by confidence:

A	B	Type	Score
EMC9	EMC2	psi-mi:“MI:0915”(physical association)	0.940
EMC2	EMC9	psi-mi:“MI:0915”(physical association)	0.940
EMC2	EMC8	psi-mi:“MI:0914”(association)	0.940
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
EMC3	EMC8	psi-mi:“MI:0914”(association)	0.730
MMGT1	EMC8	psi-mi:“MI:0914”(association)	0.730
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
EMC4	EMC8	psi-mi:“MI:0914”(association)	0.640
EMC9	EMC4	psi-mi:“MI:0914”(association)	0.640
EMC10	EMC8	psi-mi:“MI:0915”(physical association)	0.620
SCN5A	EMC9	psi-mi:“MI:0915”(physical association)	0.560
EMC6	EMC8	psi-mi:“MI:0914”(association)	0.530
EMC9	E7	psi-mi:“MI:0915”(physical association)	0.370
EMC9	OGA	psi-mi:“MI:0914”(association)	0.350
EMC3	EMC8	psi-mi:“MI:0914”(association)	0.350
EMC2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
EMC4	OSBPL8	psi-mi:“MI:0914”(association)	0.350

BioGRID (202): EMC9 (Two-hybrid), EMC9 (Affinity Capture-MS), EMC9 (Affinity Capture-MS), EMC9 (Affinity Capture-MS), EMC9 (Affinity Capture-MS), EMC9 (Affinity Capture-MS), EMC9 (Two-hybrid), EMC3 (Affinity Capture-MS), EMC2 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC6 (Affinity Capture-MS), EMC4 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), MMGT1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A4FUH1, D3ZBP4, D3ZX08, F1MH07, F1QMV3, O75843, O75865, O88202, O88512, P34605, P40935, P41226, Q002B5, Q00722, Q13488, Q14CH7, Q32L78, Q32PE2, Q3T086, Q3UHX9, Q54YG5, Q568Y2, Q5E9J8, Q5F359, Q5I0I8, Q5JTZ9, Q5U1W7, Q61IU9, Q6AYR4, Q78XR0, Q86SZ2, Q86U10, Q86VI3, Q8BHY2, Q8R1J9, Q8R307, Q8TDZ2, Q8VDP3, Q92843

Diamond homologs: O43402, O70378, Q32KL5, Q55FM0, Q5FVL2, Q5U1W7, Q9DB76, Q9W1Y1, Q9Y3B6, Q9FG71

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EMC9	“form complex”	“Endoplasmic reticulum membrane complex- EMC9 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
tail-anchored membrane protein insertion into ER membrane	8	416.1×	6e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

719 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24139193:CACT:C	acceptor_gain	1.0000
14:24139195:CT:C	acceptor_gain	1.0000
14:24139197:C:CC	acceptor_gain	1.0000
14:24139352:GTACT:G	donor_loss	1.0000
14:24139354:ACT:A	donor_loss	1.0000
14:24139356:TCACA:T	donor_loss	1.0000
14:24139357:CAC:C	donor_loss	1.0000
14:24139358:A:AC	donor_gain	1.0000
14:24139358:ACAAG:A	donor_loss	1.0000
14:24139359:C:CT	donor_gain	1.0000
14:24139359:CA:C	donor_gain	1.0000
14:24139359:CAA:C	donor_gain	1.0000
14:24139359:CAAG:C	donor_gain	1.0000
14:24139359:CAAGT:C	donor_gain	1.0000
14:24139368:AT:A	donor_gain	1.0000
14:24139450:TCCAA:T	acceptor_gain	1.0000
14:24139451:CCAA:C	acceptor_gain	1.0000
14:24139451:CCAAC:C	acceptor_gain	1.0000
14:24139452:CAA:C	acceptor_gain	1.0000
14:24139452:CAAC:C	acceptor_gain	1.0000
14:24139453:AA:A	acceptor_gain	1.0000
14:24139455:C:CC	acceptor_gain	1.0000
14:24139459:G:C	acceptor_gain	1.0000
14:24139459:G:GC	acceptor_gain	1.0000
14:24139555:A:AC	donor_gain	1.0000
14:24139556:C:CC	donor_gain	1.0000
14:24140884:CTCA:C	donor_loss	1.0000
14:24140885:TCAC:T	donor_loss	1.0000
14:24140886:CA:C	donor_loss	1.0000
14:24140887:ACCTC:A	donor_loss	1.0000

AlphaMissense

1353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24139081:A:G	W186R	0.995
14:24139081:A:T	W186R	0.995
14:24139105:G:C	H178D	0.993
14:24139079:C:A	W186C	0.992
14:24139079:C:G	W186C	0.992
14:24139112:A:C	F175L	0.992
14:24139112:A:T	F175L	0.992
14:24139114:A:G	F175L	0.992
14:24139405:A:T	V132D	0.991
14:24141117:G:T	A63D	0.991
14:24139073:G:C	N188K	0.990
14:24139073:G:T	N188K	0.990
14:24139382:A:G	W140R	0.990
14:24139382:A:T	W140R	0.990
14:24141222:C:T	G28E	0.990
14:24141266:C:A	K13N	0.990
14:24141266:C:G	K13N	0.990
14:24140920:A:C	Y82D	0.989
14:24141162:G:T	P48H	0.989
14:24141223:C:A	G28W	0.989
14:24139113:A:G	F175S	0.988
14:24140925:C:T	G80D	0.988
14:24139371:C:A	K143N	0.987
14:24139371:C:G	K143N	0.987
14:24139117:C:G	D174H	0.986
14:24140914:C:G	A84P	0.986
14:24139115:G:C	D174E	0.985
14:24139115:G:T	D174E	0.985
14:24139552:A:G	L113P	0.985
14:24139113:A:C	F175C	0.984

dbSNP variants (sampled 300 via entrez): RS1000965185 (14:24143489 C>T), RS1002072671 (14:24140373 C>A,G), RS1002140383 (14:24141642 C>A), RS1002144510 (14:24139041 A>G), RS1002210593 (14:24140382 C>T), RS1002444677 (14:24140718 G>C), RS1002810777 (14:24141841 C>T), RS1004550615 (14:24142230 A>T), RS1005251996 (14:24139808 C>A,T), RS1005283240 (14:24140141 T>C), RS1006294303 (14:24139745 C>A,G,T), RS1006556338 (14:24139803 G>A), RS1007659026 (14:24141467 C>A,G), RS1008191776 (14:24140075 C>T), RS1008633103 (14:24142298 G>A)

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: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tunicamycin	increases expression	2
aristolochic acid I	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Selenium	decreases expression, affects cotreatment	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	affects cotreatment, decreases expression, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7GC	Ubigene HEK293T EMC9 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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