EMC7

Summary

EMC7 (ER membrane protein complex subunit 7, HGNC:24301) is a protein-coding gene on chromosome 15q14, encoding Endoplasmic reticulum membrane protein complex subunit 7 (Q9NPA0). Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. It is a selective cancer dependency (DepMap: 71.5% of cell lines).

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 endoplasmic reticulum membrane. Part of EMC complex.

Source: NCBI Gene 56851 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 71.5% of screened cell lines
• MANE Select transcript: NM_020154

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24301
Approved symbol	EMC7
Name	ER membrane protein complex subunit 7
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	C11orf3
Ensembl gene	ENSG00000134153
Ensembl biotype	protein_coding
OMIM	620631
Entrez	56851

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000256545, ENST00000527822, ENST00000528949, ENST00000532113, ENST00000880067, ENST00000917774, ENST00000917775, ENST00000961768

RefSeq mRNA: 1 — MANE Select: NM_020154 NM_020154

CCDS: CCDS10032

Canonical transcript exons

ENST00000256545 — 5 exons

Exon	Start	End
ENSE00000912984	34095895	34096014
ENSE00001043239	34090317	34090455
ENSE00001043245	34088053	34088133
ENSE00001232334	34084017	34084486
ENSE00001232339	34101604	34101862

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.5240 / max 301.7031, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149222	59.4158	1827
149223	1.1082	739

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	98.03	gold quality
islet of Langerhans	UBERON:0000006	97.93	gold quality
stromal cell of endometrium	CL:0002255	97.88	gold quality
type B pancreatic cell	CL:0000169	97.84	gold quality
left adrenal gland	UBERON:0001234	97.12	gold quality
right adrenal gland	UBERON:0001233	97.05	gold quality
tendon of biceps brachii	UBERON:0008188	97.03	gold quality
male germ cell	CL:0000015	97.01	gold quality
sperm	CL:0000019	96.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.95	gold quality
right adrenal gland cortex	UBERON:0035827	96.92	gold quality
left adrenal gland cortex	UBERON:0035825	96.89	gold quality
adrenal cortex	UBERON:0001235	96.72	gold quality
spinal cord	UBERON:0002240	96.70	gold quality
hypothalamus	UBERON:0001898	96.65	gold quality
rectum	UBERON:0001052	96.59	gold quality
adrenal gland	UBERON:0002369	96.59	gold quality
thoracic aorta	UBERON:0001515	96.58	gold quality
ascending aorta	UBERON:0001496	96.56	gold quality
smooth muscle tissue	UBERON:0001135	96.54	gold quality
caudate nucleus	UBERON:0001873	96.51	gold quality
descending thoracic aorta	UBERON:0002345	96.50	gold quality
substantia nigra	UBERON:0002038	96.43	gold quality
right atrium auricular region	UBERON:0006631	96.37	gold quality
nucleus accumbens	UBERON:0001882	96.36	gold quality
putamen	UBERON:0001874	96.28	gold quality
left coronary artery	UBERON:0001626	96.27	gold quality
placenta	UBERON:0001987	96.25	gold quality
adult organism	UBERON:0007023	96.24	gold quality
right testis	UBERON:0004534	96.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	no	7.55
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3, TCF3

miRNA regulators (miRDB)

41 targeting EMC7, 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-1277-5P	100.00	73.95	5056
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4782-5P	98.35	69.33	1474

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 71.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Candidate modifier gene on the phenotypic expression of hypertrophy in patients with hyperthophic cardiomyopathy. (PMID:17165166)
• ER membrane protein complex subunit 4 (EMC4) and EMC7 support SV40 infection by promoting from the late endosome (LE) to the endoplasmic reticulum (ER) targeting of the virus. They do this by engaging LE-associated Rab7, to stabilize contact between the LE and ER. These EMC subunits also bind to the ER-resident fusion machinery component syntaxin18, which is required for SV40-arrival to the ER. (PMID:32111841)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	emc7b	ENSDARG00000012144
danio_rerio	emc7a	ENSDARG00000102983
mus_musculus	Emc7	ENSMUSG00000055943
rattus_norvegicus	Emc7	ENSRNOG00000005884
drosophila_melanogaster	EMC7	FBGN0034066
caenorhabditis_elegans		WBGENE00016439

Protein

Protein identifiers

Endoplasmic reticulum membrane protein complex subunit 7 — Q9NPA0 (reviewed: Q9NPA0)

Alternative names: ER membrane protein complex subunit 7

All UniProt accessions (3): Q9NPA0, H0YDT8, H0YDX2

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).

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the EMC7 family.

RefSeq proteins (1): NP_064539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013784	Carb-bd-like_fold	Homologous_superfamily
IPR019008	Beta_sandwich_EMC7	Domain
IPR039163	EMC7	Family

Pfam: PF09430

UniProt features (24 total): strand 12, helix 3, topological domain 2, turn 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
1LP9	X-RAY DIFFRACTION	2
2UWE	X-RAY DIFFRACTION	2.4
1B0G	X-RAY DIFFRACTION	2.5
2JCC	X-RAY DIFFRACTION	2.5
2J8U	X-RAY DIFFRACTION	2.88
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
8S9S	ELECTRON MICROSCOPY	3.6
9ZZ6	ELECTRON MICROSCOPY	4.16
6Z3W	ELECTRON MICROSCOPY	6.4
9C7V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPA0-F1	74.54	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, chr15q14, ONKEN_UVEAL_MELANOMA_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, CUI_TCF21_TARGETS_2_DN, ATGTCAC_MIR489, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, LAIHO_COLORECTAL_CANCER_SERRATED_UP, PAX6_01, GOCC_MEMBRANE_PROTEIN_COMPLEX

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 (3): carbohydrate binding (GO:0030246), protein binding (GO:0005515), membrane insertase activity (GO:0032977)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), EMC complex (GO:0072546), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein insertion into ER membrane	2
binding	2
establishment of protein localization to membrane	1
protein carrier activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	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

1022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMC7	EMC4	Q5J8M3	869
EMC7	EMC1	Q8N766	864
EMC7	MMGT1	Q8N4V1	852
EMC7	EMC3	Q9P0I2	827
EMC7	LTAP1	Q9BWL3	818
EMC7	EMC6	Q9BV81	806
EMC7	EMC10	Q5UCC4	786
EMC7	EMC8	O43402	748
EMC7	EMC9	Q9Y3B6	747
EMC7	EMC2	Q15006	710
EMC7	CHMP2A	O43633	707
EMC7	PSMB4	P28070	640
EMC7	PSMB2	P31145	634
EMC7	TMEM147	Q9BVK8	587
EMC7	VPS29	Q9UBQ0	540

IntAct

174 interactions, top by confidence:

A	B	Type	Score
EMC2	EMC8	psi-mi:“MI:0914”(association)	0.940
EMC8	EMC2	psi-mi:“MI:0914”(association)	0.940
EMC2	EMC10	psi-mi:“MI:0914”(association)	0.800
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
TMED9	TMED10	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
EMC1	EMC8	psi-mi:“MI:0914”(association)	0.640

BioGRID (276): EMC9 (Affinity Capture-MS), UBQLN2 (Affinity Capture-MS), EMC8 (Affinity Capture-MS), EMC2 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), EMC6 (Affinity Capture-MS), MMGT1 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC7 (Affinity Capture-MS)

ESM2 similar proteins: A5D8P8, A5PJA8, A6QLP7, A7E2Z9, A9SV59, B5DDX6, E2RQ08, F1QR43, F1R777, F4JVN6, O12940, O18756, O64614, O94923, P04843, P07153, P16967, P43307, P45433, P51571, P53815, Q04499, Q05AW9, Q07984, Q0IHY5, Q0J6P7, Q2M146, Q2TBX5, Q3UFM5, Q4R4T0, Q4R5V2, Q5R4X4, Q5REH6, Q5RFB6, Q5TYV0, Q5ZJT0, Q62186, Q6P7K5, Q7ZV50, Q8BXQ2

Diamond homologs: A5PJA8, Q0IHY5, Q4R5V2, Q5TYV0, Q8WQG1, Q9EP72, Q9NPA0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EMC7	“form complex”	“Endoplasmic reticulum membrane complex- EMC9 variant”	binding
EMC7	“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 159 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
COPI-dependent Golgi-to-ER retrograde traffic	6	6.6×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
tail-anchored membrane protein insertion into ER membrane	9	62.4×	2e-12
ERAD pathway	8	10.7×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

757 predictions. Top by Δscore:

Variant	Effect	Δscore
15:34085533:T:TA	donor_gain	1.0000
15:34088052:CCCGT:C	donor_gain	1.0000
15:34088130:TAAC:T	acceptor_gain	1.0000
15:34088130:TAACC:T	acceptor_loss	1.0000
15:34088131:AACC:A	acceptor_loss	1.0000
15:34088132:ACCT:A	acceptor_loss	1.0000
15:34088134:C:CA	acceptor_loss	1.0000
15:34088135:T:C	acceptor_loss	1.0000
15:34090469:A:C	acceptor_gain	1.0000
15:34095889:CCTCA:C	donor_loss	1.0000
15:34095890:CTCA:C	donor_loss	1.0000
15:34095891:TCAC:T	donor_loss	1.0000
15:34095892:CA:C	donor_loss	1.0000
15:34095894:C:CG	donor_loss	1.0000
15:34095894:CCT:C	donor_gain	1.0000
15:34096010:CTGTC:C	acceptor_gain	1.0000
15:34096014:CCT:C	acceptor_loss	1.0000
15:34096015:C:CC	acceptor_gain	1.0000
15:34096015:CTG:C	acceptor_loss	1.0000
15:34096016:T:C	acceptor_loss	1.0000
15:34101602:A:AC	donor_gain	1.0000
15:34101603:C:CC	donor_gain	1.0000
15:34101606:A:AC	donor_gain	1.0000
15:34101766:T:TA	donor_gain	1.0000
15:34084483:TTTC:T	acceptor_gain	0.9900
15:34084484:TTCC:T	acceptor_loss	0.9900
15:34084485:TCCT:T	acceptor_loss	0.9900
15:34084486:CCTG:C	acceptor_loss	0.9900
15:34084487:C:CC	acceptor_gain	0.9900
15:34084487:CTG:C	acceptor_loss	0.9900

AlphaMissense

1569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:34088105:A:T	I175K	1.000
15:34088114:G:C	P172R	1.000
15:34088117:A:T	L171H	1.000
15:34088123:A:C	M169R	1.000
15:34088123:A:T	M169K	1.000
15:34095994:A:T	V86D	1.000
15:34096000:A:G	F84S	1.000
15:34084431:G:A	S211F	0.999
15:34084434:A:T	V210D	0.999
15:34084474:A:G	S197P	0.999
15:34088096:A:T	L178H	0.999
15:34088105:A:C	I175R	0.999
15:34088114:G:T	P172H	0.999
15:34088117:A:C	L171R	0.999
15:34088120:A:T	V170D	0.999
15:34088126:A:C	M168R	0.999
15:34088126:A:T	M168K	0.999
15:34090347:C:A	W155C	0.999
15:34090347:C:G	W155C	0.999
15:34090399:A:T	L138H	0.999
15:34090453:G:T	A120E	0.999
15:34095922:A:T	V110E	0.999
15:34095925:C:G	R109P	0.999
15:34095999:A:C	F84L	0.999
15:34095999:A:T	F84L	0.999
15:34096001:A:G	F84L	0.999
15:34101614:C:G	G76R	0.999
15:34101657:C:A	W61C	0.999
15:34101657:C:G	W61C	0.999
15:34101659:A:G	W61R	0.999

dbSNP variants (sampled 300 via entrez): RS1000229375 (15:34093603 G>A), RS1000644837 (15:34087234 C>T), RS1000861747 (15:34093361 C>A,G,T), RS1001014061 (15:34099153 T>A,C), RS1001105038 (15:34093532 A>G), RS1001325299 (15:34100517 C>T), RS1001545947 (15:34099835 G>A,C), RS1001561993 (15:34097565 G>A), RS1001724441 (15:34092997 T>A,C), RS1001988441 (15:34097275 C>T), RS1002515518 (15:34098779 C>A,G,T), RS1002726343 (15:34101414 C>T), RS1002751173 (15:34101103 T>G), RS1002960335 (15:34098430 A>G), RS1003330136 (15:34095757 G>A)

Disease associations

OMIM: gene MIM:620631 | 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
GCST010725_22	Malaria	3.000000e-06
GCST010725_37	Malaria	3.000000e-06
GCST010725_54	Malaria	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
bisphenol A	decreases expression, affects expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Valproic Acid	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, increases expression	1
bleomycetin	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
chloropicrin	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Ivermectin	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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