EMC8

Summary

EMC8 (ER membrane protein complex subunit 8, HGNC:7864) is a protein-coding gene on chromosome 16q24.1, encoding ER membrane protein complex subunit 8 (O43402). 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 Golgi apparatus and endoplasmic reticulum. Part of EMC complex.

Source: NCBI Gene 10328 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_006067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7864
Approved symbol	EMC8
Name	ER membrane protein complex subunit 8
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FAM158B
Ensembl gene	ENSG00000131148
Ensembl biotype	protein_coding
OMIM	604886
Entrez	10328

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000253457, ENST00000435200, ENST00000595980, ENST00000596852, ENST00000597291, ENST00000600807, ENST00000870911, ENST00000870912, ENST00000965667, ENST00000965668, ENST00000965669, ENST00000965670, ENST00000965671

RefSeq mRNA: 2 — MANE Select: NM_006067 NM_001142288, NM_006067

CCDS: CCDS10954, CCDS45541

Canonical transcript exons

ENST00000253457 — 5 exons

Exon	Start	End
ENSE00000695664	85788974	85789050
ENSE00000945795	85781211	85781280
ENSE00001880830	85799065	85799544
ENSE00003474732	85778624	85779867
ENSE00003546372	85780379	85780473

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.8505 / max 119.9877, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158416	26.2887	1816
158415	2.3417	1176
158417	1.1217	842
158413	0.7387	503
158414	0.3597	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.16	gold quality
secondary oocyte	CL:0000655	97.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.32	gold quality
mucosa of transverse colon	UBERON:0004991	90.03	gold quality
granulocyte	CL:0000094	89.77	gold quality
stromal cell of endometrium	CL:0002255	89.71	gold quality
sperm	CL:0000019	89.66	gold quality
left testis	UBERON:0004533	89.61	gold quality
colonic mucosa	UBERON:0000317	89.59	gold quality
right testis	UBERON:0004534	89.09	gold quality
adult organism	UBERON:0007023	89.03	gold quality
endothelial cell	CL:0000115	88.95	silver quality
gastrocnemius	UBERON:0001388	88.91	gold quality
palpebral conjunctiva	UBERON:0001812	88.63	gold quality
parietal pleura	UBERON:0002400	88.60	gold quality
heart right ventricle	UBERON:0002080	88.56	gold quality
eye	UBERON:0000970	88.51	gold quality
visceral pleura	UBERON:0002401	88.49	gold quality
gingival epithelium	UBERON:0001949	88.46	gold quality
testis	UBERON:0000473	88.44	gold quality
heart left ventricle	UBERON:0002084	88.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.36	gold quality
cardiac ventricle	UBERON:0002082	88.29	gold quality
muscle of leg	UBERON:0001383	88.13	gold quality
pigmented layer of retina	UBERON:0001782	88.08	gold quality
retina	UBERON:0000966	88.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.05	gold quality
amniotic fluid	UBERON:0000173	87.98	gold quality
pleura	UBERON:0000977	87.90	gold quality
monocyte	CL:0000576	87.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34
E-MTAB-6142	no	227.27
E-HCAD-13	no	3.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting EMC8, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6892-3P	99.68	66.40	1178

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	emc8	ENSDARG00000017093
mus_musculus	Emc8	ENSMUSG00000031819
rattus_norvegicus	Emc8	ENSRNOG00000017654
drosophila_melanogaster	EMC8-9	FBGN0034791
caenorhabditis_elegans	F25H2.4	WBGENE00009118

Paralogs (1): EMC9 (ENSG00000100908)

Protein

Protein identifiers

ER membrane protein complex subunit 8 — O43402 (reviewed: O43402)

Alternative names: Neighbor of COX4, Protein FAM158B

All UniProt accessions (3): O43402, M0R1B0, Q53Y03

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.

Tissue specificity. Expressed in liver, pancreas, heart, lung, kidney, brain, skeletal muscle, and placenta. Expression levels are highest in pancreas and moderate in heart, skeletal muscle, and placenta.

Similarity. Belongs to the EMC8/EMC9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43402-1	1	yes
O43402-2	2

RefSeq proteins (2): NP_001135760, NP_006058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005366	EMC8/9	Family
IPR037518	MPN	Domain

Pfam: PF03665

UniProt features (24 total): strand 12, helix 7, turn 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8J0O	ELECTRON MICROSCOPY	3.32
7ADO	ELECTRON MICROSCOPY	3.39
6WW7	ELECTRON MICROSCOPY	3.4
8EOI	ELECTRON MICROSCOPY	3.4
8J0N	ELECTRON MICROSCOPY	3.47
7ADP	ELECTRON MICROSCOPY	3.6
8S9S	ELECTRON MICROSCOPY	3.6
9ZZ6	ELECTRON MICROSCOPY	4.16
9C7V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43402-F1	91.60	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, TGACCTY_ERR1_Q2, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GCM_NF2, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, DANG_BOUND_BY_MYC, BURTON_ADIPOGENESIS_4, CUI_TCF21_TARGETS_2_UP, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE

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 (6): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020), EMC complex (GO:0072546)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein insertion into ER membrane	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	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

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMC8	COX4I1	P13073	964
EMC8	COX4I2	Q96KJ9	949
EMC8	EMC4	Q5J8M3	823
EMC8	MMGT1	Q8N4V1	823
EMC8	EMC3	Q9P0I2	794
EMC8	EMC1	Q8N766	774
EMC8	EMC2	Q15006	771
EMC8	EMC7	Q9NPA0	748
EMC8	EMC6	Q9BV81	735
EMC8	EMC10	Q5UCC4	708
EMC8	CLMB	Q96GX8	626
EMC8	GINS2	Q9Y248	570
EMC8	DDX46	Q7L014	427
EMC8	FAM8A1	Q9UBU6	391
EMC8	BSPRY	Q5W0U4	387

IntAct

135 interactions, top by confidence:

A	B	Type	Score
EMC2	EMC8	psi-mi:“MI:0915”(physical association)	0.940
EMC2	EMC8	psi-mi:“MI:0914”(association)	0.940
EMC8	EMC2	psi-mi:“MI:0915”(physical association)	0.940
EMC8	EMC2	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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (305): EMC8 (Two-hybrid), EMC8 (Affinity Capture-RNA), EMC8 (Affinity Capture-RNA), EMC8 (Affinity Capture-MS), UBQLN2 (Affinity Capture-MS), EMC2 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), EMC6 (Affinity Capture-MS), MMGT1 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC8 (Affinity Capture-MS), EMC8 (Affinity Capture-MS), EMC8 (Affinity Capture-MS)

ESM2 similar proteins: A2AWA9, A2RSQ0, A6QQ21, A7TX81, B1H2N3, B5DGH9, B5KFI0, O43242, O43402, O70378, O88545, P11029, P11497, P14685, P23514, P60228, P60229, Q05AY2, Q07G98, Q0IIL1, Q13085, Q1LUA8, Q28559, Q2KJ46, Q32KL5, Q3T102, Q4R4U1, Q4R518, Q4R6G8, Q5FVL2, Q5R5F8, Q5R8K9, Q5R8N4, Q5REY0, Q5SWU9, Q5ZIA5, Q5ZLA5, Q641X8, Q6DRI1, Q6NUC2

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EMC8	“form complex”	“Endoplasmic reticulum membrane complex, EMC8 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	31.3×	6e-05
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	5	20.2×	3e-04
Maturation of spike protein	6	19.2×	7e-05
Maturation of DENV proteins	6	15.3×	2e-04
Regulation of RAS by GAPs	5	11.7×	2e-03
ER-Phagosome pathway	5	7.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
tail-anchored membrane protein insertion into ER membrane	8	73.4×	2e-11
autophagosome assembly	7	15.4×	6e-05
ERAD pathway	8	14.2×	2e-05
protein N-linked glycosylation	5	12.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1013 predictions. Top by Δscore:

Variant	Effect	Δscore
16:85779864:GTCA:G	acceptor_gain	1.0000
16:85779866:CA:C	acceptor_gain	1.0000
16:85779868:C:CC	acceptor_gain	1.0000
16:85780374:CTCA:C	donor_gain	1.0000
16:85780377:A:AC	donor_gain	1.0000
16:85780378:C:CG	donor_gain	1.0000
16:85780378:CTG:C	donor_gain	1.0000
16:85780378:CTGG:C	donor_gain	1.0000
16:85781206:CTTA:C	donor_loss	1.0000
16:85781207:TTA:T	donor_loss	1.0000
16:85781208:TACCA:T	donor_loss	1.0000
16:85781209:A:AC	donor_gain	1.0000
16:85781210:C:CC	donor_gain	1.0000
16:85781210:C:CT	donor_loss	1.0000
16:85789046:TCAAT:T	acceptor_gain	1.0000
16:85789047:CAAT:C	acceptor_gain	1.0000
16:85789047:CAATC:C	acceptor_gain	1.0000
16:85789048:AATCT:A	acceptor_loss	1.0000
16:85789049:ATCT:A	acceptor_loss	1.0000
16:85789050:TCTGA:T	acceptor_loss	1.0000
16:85789051:C:CA	acceptor_loss	1.0000
16:85789051:C:CC	acceptor_gain	1.0000
16:85789052:T:C	acceptor_loss	1.0000
16:85799060:CTTA:C	donor_loss	1.0000
16:85799061:TTA:T	donor_loss	1.0000
16:85799063:ACCAG:A	donor_loss	1.0000
16:85799064:C:CT	donor_loss	1.0000
16:85779863:AGTCA:A	acceptor_gain	0.9900
16:85779865:TCA:T	acceptor_gain	0.9900
16:85779866:CAC:C	acceptor_gain	0.9900

AlphaMissense

1392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:85779744:G:C	N199K	1.000
16:85779744:G:T	N199K	1.000
16:85779750:C:A	W197C	1.000
16:85779750:C:G	W197C	1.000
16:85779752:A:G	W197R	1.000
16:85779752:A:T	W197R	1.000
16:85779772:A:G	L190P	1.000
16:85779776:G:C	H189D	1.000
16:85779787:T:A	D185V	1.000
16:85779788:C:G	D185H	1.000
16:85780401:A:G	W151R	1.000
16:85780401:A:T	W151R	1.000
16:85789005:A:C	Y93D	1.000
16:85799075:G:T	A74D	1.000
16:85799112:G:C	H62D	1.000
16:85799213:C:T	G28E	1.000
16:85799214:C:A	G28W	1.000
16:85799214:C:G	G28R	1.000
16:85799214:C:T	G28R	1.000
16:85799257:C:A	K13N	1.000
16:85799257:C:G	K13N	1.000
16:85779751:C:G	W197S	0.999
16:85779774:G:C	H189Q	0.999
16:85779774:G:T	H189Q	0.999
16:85779781:T:A	D187V	0.999
16:85779782:C:A	D187Y	0.999
16:85779782:C:G	D187H	0.999
16:85779783:G:C	F186L	0.999
16:85779783:G:T	F186L	0.999
16:85779784:A:G	F186S	0.999

dbSNP variants (sampled 300 via entrez): RS1000092520 (16:85780079 T>C), RS1000109301 (16:85782806 T>A), RS1000155909 (16:85779323 A>C), RS1000235586 (16:85794967 A>T), RS1000266894 (16:85795095 A>C), RS1000411826 (16:85783654 C>G), RS1000462389 (16:85799606 A>C), RS1000558249 (16:85795853 G>A,C), RS1000589380 (16:85796011 C>T), RS1000590328 (16:85779924 C>T), RS1000668326 (16:85782769 C>T), RS1000767125 (16:85800282 C>T), RS1000786364 (16:85787558 G>A), RS1000831746 (16:85791228 T>C), RS1000834522 (16:85799441 C>A,G,T)

Disease associations

OMIM: gene MIM:604886 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004606_20	Eosinophil count	7.000000e-11
GCST004624_2	Sum eosinophil basophil counts	9.000000e-11
GCST90002381_100	Eosinophil count	6.000000e-13
GCST90002382_404	Eosinophil percentage of white cells	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1R5	Abcam HeLa EMC8 KO	Cancer cell line	Female
CVCL_D7GB	Ubigene HEK293T EMC8 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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