EMC6

Summary

EMC6 (ER membrane protein complex subunit 6, HGNC:28430) is a protein-coding gene on chromosome 17p13.2, encoding ER membrane protein complex subunit 6 (Q9BV81). 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: 16.7% of cell lines).

Contributes to membrane insertase activity. Involved in autophagosome assembly; 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 and omegasome membrane. Part of EMC complex.

Source: NCBI Gene 83460 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 14 total
• GTEx eGene: eQTL in 7 tissues, sQTL in 3 (q < 0.05)
• Cancer dependency (DepMap): dependent in 16.7% of screened cell lines
• Constraint (gnomAD): pLI 0.78 (intermediate), LOEUF 0.73 (unconstrained)
• MANE Select transcript: NM_031298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28430
Approved symbol	EMC6
Name	ER membrane protein complex subunit 6
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC2963, RAB5IFL
Ensembl gene	ENSG00000127774
Ensembl biotype	protein_coding
OMIM	620261
Entrez	83460

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

MANE Select: ENST00000248378

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000248378, ENST00000397133, ENST00000890763, ENST00000890764, ENST00001138009

RefSeq mRNA: 2 — MANE Select: NM_031298 NM_001014764, NM_031298

CCDS: CCDS11033

Canonical transcript exons

ENST00000248378 — 2 exons

Exon	Start	End
ENSE00001308926	3668812	3668899
ENSE00002752197	3669098	3669665

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.9518 / max 375.5162, expressed in 1822 samples.

Highest expression (Bgee): hindlimb stylopod muscle, gastrocnemius, muscle of leg, muscle organ, skeletal muscle tissue of rectus abdominis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EMC6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	9.8e-08	-0.73	17:3668945:C:T
Testis	eqtl	4.5e-06	+0.22	17:3676705:TG:T
Cells Cultured fibroblasts	sqtl	8.8e-04	-0.69	17:3668945:C:T
Artery Aorta	eqtl	1.9e-03	-0.25	17:3134805:G:T
Nerve Tibial	sqtl	7.3e-03	-0.36	17:3350291:C:T
Skin Not Sun Exposed Suprapubic	eqtl	3.6e-02	-0.19	17:3491475:G:A
Colon Transverse	eqtl	3.6e-02	-0.10	17:3726573:G:A
Esophagus Muscularis	eqtl	4.4e-02	-0.28	17:3057465:C:T
Cells Cultured fibroblasts	eqtl	4.8e-02	-0.20	17:3161431:A:G
Brain Spinal cord cervical c-1	eqtl	5.0e-02	-0.68	17:3004868:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
158879	78.9518	1822

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.22	gold quality
gastrocnemius	UBERON:0001388	97.21	gold quality
muscle of leg	UBERON:0001383	96.61	gold quality
muscle organ	UBERON:0001630	96.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.84	gold quality
apex of heart	UBERON:0002098	95.60	gold quality
vastus lateralis	UBERON:0001379	95.43	silver quality
quadriceps femoris	UBERON:0001377	95.39	gold quality
heart left ventricle	UBERON:0002084	95.29	gold quality
cardiac ventricle	UBERON:0002082	95.20	gold quality
diaphragm	UBERON:0001103	95.17	silver quality
biceps brachii	UBERON:0001507	95.01	gold quality
skeletal muscle tissue	UBERON:0001134	94.79	gold quality
right testis	UBERON:0004534	94.73	gold quality
right atrium auricular region	UBERON:0006631	94.64	gold quality
deltoid	UBERON:0001476	94.57	silver quality
triceps brachii	UBERON:0001509	94.56	gold quality
gluteal muscle	UBERON:0002000	94.53	gold quality
left testis	UBERON:0004533	94.52	gold quality
heart right ventricle	UBERON:0002080	94.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.33	gold quality
mucosa of transverse colon	UBERON:0004991	94.24	gold quality
adult organism	UBERON:0007023	93.99	gold quality
right adrenal gland cortex	UBERON:0035827	93.92	gold quality
right adrenal gland	UBERON:0001233	93.90	gold quality
cardiac atrium	UBERON:0002081	93.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.78	gold quality
left adrenal gland	UBERON:0001234	93.61	gold quality
left adrenal gland cortex	UBERON:0035825	93.54	gold quality
heart	UBERON:0000948	93.52	gold quality
right lobe of liver	UBERON:0001114	93.27	gold quality
body of tongue	UBERON:0011876	93.22	gold quality
adrenal cortex	UBERON:0001235	93.05	gold quality
body of stomach	UBERON:0001161	93.04	gold quality
lower esophagus mucosa	UBERON:0035834	93.00	gold quality
testis	UBERON:0000473	92.76	gold quality
muscle tissue	UBERON:0002385	92.74	gold quality
granulocyte	CL:0000094	92.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.27	gold quality
lower esophagus	UBERON:0013473	92.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.22	gold quality
esophagus mucosa	UBERON:0002469	92.13	gold quality
tibialis anterior	UBERON:0001385	92.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.86	gold quality
esophagus	UBERON:0001043	91.78	gold quality
putamen	UBERON:0001874	91.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.54	gold quality
spinal cord	UBERON:0002240	91.37	gold quality
anterior cingulate cortex	UBERON:0009835	91.35	gold quality
cingulate cortex	UBERON:0003027	91.33	gold quality
nephron tubule	UBERON:0001231	91.30	silver quality
transverse colon	UBERON:0001157	91.27	gold quality
metanephros cortex	UBERON:0010533	91.25	gold quality
adrenal gland	UBERON:0002369	91.22	gold quality
amygdala	UBERON:0001876	91.11	gold quality
gingival epithelium	UBERON:0001949	91.11	silver quality
adult mammalian kidney	UBERON:0000082	91.10	gold quality
monocyte	CL:0000576	91.07	gold quality
leukocyte	CL:0000738	91.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.97	gold quality
caudate nucleus	UBERON:0001873	90.94	gold quality
mononuclear cell	CL:0000842	90.91	gold quality
prefrontal cortex	UBERON:0000451	90.83	gold quality
right frontal lobe	UBERON:0002810	90.75	gold quality
epithelium of esophagus	UBERON:0001976	90.61	gold quality
esophagus squamous epithelium	UBERON:0006920	90.54	gold quality
cortex of kidney	UBERON:0001225	90.53	gold quality
tongue	UBERON:0001723	90.50	gold quality
metanephros	UBERON:0000081	90.43	gold quality
ventricular zone	UBERON:0003053	90.31	gold quality
nucleus accumbens	UBERON:0001882	90.26	gold quality
left coronary artery	UBERON:0001626	90.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.21	gold quality
body of pancreas	UBERON:0001150	90.13	gold quality
metanephric glomerulus	UBERON:0004736	90.13	silver quality
gingiva	UBERON:0001828	90.10	silver quality
small intestine Peyer’s patch	UBERON:0003454	90.02	gold quality
omental fat pad	UBERON:0010414	90.00	gold quality
peritoneum	UBERON:0002358	89.99	gold quality
colon	UBERON:0001155	89.93	gold quality
skin of abdomen	UBERON:0001416	89.88	gold quality
minor salivary gland	UBERON:0001830	89.86	gold quality
coronary artery	UBERON:0001621	89.83	gold quality
renal glomerulus	UBERON:0000074	89.81	silver quality
large intestine	UBERON:0000059	89.80	gold quality
fundus of stomach	UBERON:0001160	89.77	gold quality
mucosa of stomach	UBERON:0001199	89.76	gold quality
stomach	UBERON:0000945	89.75	gold quality
mouth mucosa	UBERON:0003729	89.74	gold quality
right coronary artery	UBERON:0001625	89.71	gold quality
left uterine tube	UBERON:0001303	89.70	gold quality
neocortex	UBERON:0001950	89.69	gold quality
adenohypophysis	UBERON:0002196	89.61	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.60	gold quality
skin of leg	UBERON:0001511	89.42	gold quality
frontal cortex	UBERON:0001870	89.42	gold quality
substantia nigra	UBERON:0002038	89.42	gold quality
spleen	UBERON:0002106	89.41	gold quality
nasal cavity epithelium	UBERON:0005384	89.34	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.07

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	132.6	not detected
Thalamus	tissue	71.5
Pons	tissue	70.2
Superior colliculi	tissue	70.0
Cerebral cortex	tissue	68.1	low
Somatosensory cortex	tissue	68.1
Midbrain	tissue	63.6
Hippocampal formation	tissue	59.6
Medulla oblongata	tissue	59.2
Occipital cortex	tissue	57.5
Motor cortex	tissue	56.5
Tongue	tissue	56.5
Cerebellum	tissue	56.4	not detected
Putamen	tissue	55.9
Spinal cord	tissue	55.7
Entorhinal cortex	tissue	55.0
Substantia nigra	tissue	54.1
Hypothalamus	tissue	53.0
Temporal cortex	tissue	52.9
Retrosplenial and cingulate cortex	tissue	52.4
Septum	tissue	52.1
Prefrontal cortex	tissue	50.9
Basal ganglia	tissue	50.2	not detected
Retrosplenial cortex	tissue	49.6
Ventral forebrain	tissue	48.5
Periaqueductal gray	tissue	46.2
Corpus callosum	tissue	44.3
Amygdala	tissue	43.8
Insular cortex	tissue	43.7
Frontal cortex	tissue	42.0
Olfactory bulb	tissue	37.7
Caudate putamen	tissue	37.3
Choroid plexus	tissue	32.2
Vagina	tissue	28.9	not detected
Bone marrow	tissue	28.7	low
Pituitary gland	tissue	26.8
Liver	tissue	23.8	not detected
Heart muscle	tissue	23.0	medium
Stomach 1	tissue	21.9	medium
Locus coeruleus	tissue	21.6
Hippocampus	tissue	20.8	low
Nucleus accumbens	tissue	19.8
Testis	tissue	19.1	medium
Duodenum	tissue	18.8	low
Postcentral gyrus	tissue	18.8
Salivary gland	tissue	18.5	not detected
Pancreas	tissue	18.2	low
Small intestine	tissue	17.9	medium
Colon	tissue	17.7	medium
Parathyroid gland	tissue	17.4	not detected
Kidney	tissue	17.4	medium
Adipose tissue	tissue	16.7	not detected
Retina	tissue	16.0
Adrenal gland	tissue	15.5	low
Thymus	tissue	14.5
Urinary bladder	tissue	13.8	low
Appendix	tissue	13.8	medium
Prostate	tissue	13.5	not detected
Spleen	tissue	13.1	not detected
Breast	tissue	12.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (59.6), Ventral spinal cord (55.7), Dorsal spinal cord (52.4), Ventral hippocampus (51.5), Subiculum (47.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting EMC6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

20 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-503-5P	97.87	66.83	575
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-4694-5P	94.62	65.39	532

Functional genomics

gnomAD constraint: pLI 0.778, LOEUF 0.734, missense Z 0.984 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000248378 — one region, missense o/e 0.78. DepMap (CRISPR cell-line fitness): dependent in 16.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): EJM (-1.533), ONE58 (-1.416), WSU-NHL (-1.402), UPMD1 (-1.284), BHT-101 (-1.283), C8166 (-1.221), MEC-1 (-1.215), SKNO-1 (-1.212), NB-4 (-1.211), 647-V (-1.186), THP-1 (-1.178), UM-RC-3 (-1.17), SCCOHT-1 (-1.164), OCI-LY18 (-1.133), Hs 944.T (-1.131).

Literature-anchored findings (GeneRIF, showing 6)

• Endoplasmic membrane protein complex subunit 6 (EMC6) interacted with both RAB5A and BECN1/Beclin 1 and colocalized with the omegasome marker ZFYVE1/DFCP1. (PMID:23182941)
• This is the first study to show that EMC6 induces cell death in gastric cancer cells. The molecular mechanism of how EMC6 functions as a tumor suppressor needs to be further explored. (PMID:28648145)
• The expression level of EMC-6 is significantly elevated in cervical cancer, without significant correlation with Beclin1 and Rab5a. (PMID:28742203)
• Adenovirus-mediated ectopic overexpression of EMC6 (Ad5-EMC6) decreases the activity of ERK1/2, down-regulates the levels of BCL-2 and increases the ratio of BAX/BCL-2. Ad5-EMC6 mediates anti-tumor activity through the mitochondrial apoptosis pathway. Ad5-EMC6 enhances the sensitivity of gastric cancer cells to the etoposide. (PMID:30982575)
• EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis. (PMID:33177505)
• Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression. (PMID:38445807)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	emc6	ENSDARG00000035282
mus_musculus	Emc6	ENSMUSG00000047260
rattus_norvegicus	Emc6	ENSRNOG00000019352
drosophila_melanogaster	EMC6	FBGN0039259
caenorhabditis_elegans		WBGENE00017999

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913298) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased hematocrit	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZCG8	98.2%	Diamond
Xenopus laevis	Q68EU8	98.2%	Diamond
Xenopus tropicalis	Q6GLC5	98.2%	Diamond
Dictyostelium discoideum	Q1ZXH4	37.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
P2RX5-TAX1BP3	ncRNA	100533970
CTNS	protein-coding	1497
SHPK	protein-coding	23729
TAX1BP3	protein-coding	30851
ITGAE	protein-coding	3682
P2RX5	protein-coding	5026
NCBP3	protein-coding	55421
HASPIN	protein-coding	83903
TRPV1	protein-coding	7442

Protein

Protein identifiers

ER membrane protein complex subunit 6 — Q9BV81 (reviewed: Q9BV81)

Alternative names: Transmembrane protein 93

All UniProt accessions (1): Q9BV81

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 EMC6 family.

RefSeq proteins (2): NP_001014764, NP_112588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008504	Emc6	Family
IPR029008	EMC6-like	Family

Pfam: PF07019

UniProt features (19 total): helix 6, topological domain 4, transmembrane region 3, mutagenesis site 2, initiator methionine 1, chain 1, strand 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
8J0O	cryo-EM structure of human EMC and VDAC	ELECTRON MICROSCOPY	3.32
7ADO	Cryo-EM structure of human ER membrane protein complex in lipid nanodiscs	ELECTRON MICROSCOPY	3.39
6WW7	Structure of the human ER membrane protein complex in a lipid nanodisc	ELECTRON MICROSCOPY	3.4
8EOI	Structure of a human EMC:human Cav1.2 channel complex in GDN detergent	ELECTRON MICROSCOPY	3.4
8J0N	cryo-EM structure of human EMC	ELECTRON MICROSCOPY	3.47
7ADP	Cryo-EM structure of human ER membrane protein complex in GDN detergent	ELECTRON MICROSCOPY	3.6
8S9S	Structure of the human ER membrane protein complex (EMC) in GDN	ELECTRON MICROSCOPY	3.6
9ZZ6	The ER membrane protein complex acts as a chaperone to promote voltage-gated calcium …	ELECTRON MICROSCOPY	4.16
6Z3W	Human ER membrane protein complex	ELECTRON MICROSCOPY	6.4
9C7V	Structure of the human BOS:human EMC complex in GDN	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV81-F1	82.32	0.46

Human Protein Atlas

Protein class: Transporters, Primary Active Transporters, Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): centrosome; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
N-acetylalanine	2

Mutagenesis-validated functional residues (2)

Position	Phenotype
27	no effect on emc assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the emc.
31	no effect on emc assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the emc.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 138 (showing top): TSENG_IRS1_TARGETS_UP, GOBP_VACUOLE_ORGANIZATION, PAL_PRMT5_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GGGTGGRR_PAX4_03, YY1_Q6, GOBP_MACROAUTOPHAGY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ORGANELLE_ASSEMBLY, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (3): autophagosome assembly (GO:0000045), 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): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), EMC complex (GO:0072546), omegasome membrane (GO:1903349), endoplasmic reticulum (GO:0005783)

GO top-level categories

23 GO namespaces:

Category	Terms
protein insertion into ER membrane	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
binding	1
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
bounding membrane of organelle	1
omegasome	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
autophagosome assembly	BP	mutant phenotype
protein insertion into ER membrane by stop-transfer membrane-anchor sequence	BP	direct assay
tail-anchored membrane protein insertion into ER membrane	BP	direct assay
EMC complex	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay
membrane	CC	direct assay
omegasome membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,480 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMC6	MMGT1	Q8N4V1	850
EMC6	EMC3	Q9P0I2	848
EMC6	EMC4	Q5J8M3	842
EMC6	EMC1	Q8N766	836
EMC6	EMC2	Q15006	814
EMC6	EMC8	O43402	786
EMC6	EMC7	Q9NPA0	779
EMC6	EMC9	Q9Y3B6	768
EMC6	EMC10	Q5UCC4	766
EMC6	OXA1L	Q15070	646
EMC6	GET1	O00258	640
EMC6	TMCO1	Q9UM00	587
EMC6	GET3	O43681	548
EMC6	SEC61A1	P38378	547
EMC6	CAMLG	P49069	495

IntAct

Human interaction partners of EMC6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
MMGT1	physical association	0.810	4
AQP6	physical association	0.560	3
AQP9	physical association	0.560	3
CD79A	physical association	0.560	3
EBP	physical association	0.560	3
ERGIC3	physical association	0.560	3
FAM209A	physical association	0.560	3
MFSD14B	physical association	0.560	3
MMD	physical association	0.560	3
MUC1	physical association	0.560	3
PDZK1IP1	physical association	0.560	3
SLC10A6	physical association	0.560	3
SLC39A2	physical association	0.560	3
SLC7A1	physical association	0.560	3
TLCD4	physical association	0.560	3
TMEM14B	physical association	0.560	3
TMEM237	physical association	0.560	3
EMC8	association	0.530	2

BioGRID (100 interactions; top human partners by supporting records): EMC2 (Affinity Capture-MS; 4 records), MMGT1 (Affinity Capture-MS; 4 records), EMC7 (Affinity Capture-MS; 3 records), EMC3 (Affinity Capture-MS; 2 records), EMC8 (Affinity Capture-MS; 2 records), EMC9 (Affinity Capture-MS; 2 records), HLA-DRB1 (Affinity Capture-MS; 2 records), RNF149 (Affinity Capture-MS; 2 records), TMEM237 (Proximity Label-MS; 2 records), AQP6 (Two-hybrid), AQP9 (Two-hybrid), ATP6AP1 (Negative Genetic), C4orf32 (Affinity Capture-MS), CCDC47 (Affinity Capture-MS), CD79A (Two-hybrid)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
EMC6	“form complex”	“Endoplasmic reticulum membrane complex- EMC9 variant”	binding
EMC6	“form complex”	“Endoplasmic reticulum membrane complex, EMC8 variant”	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
ER membrane protein complex (EMC8)	9	EMC6, MMGT1, EMC1, EMC10, EMC2, EMC3, EMC4, EMC7, EMC8
ER membrane protein complex (EMC9)	9	EMC4, EMC6, EMC9, MMGT1, EMC1, EMC10, EMC2, EMC7, EMC3

Disease & clinical

Genetic variants

Variant evidence for EMC6: 14 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 64):

Position(s)	Effect	Δscore	Sites
17:3668870	donor_gain	0.9900
17:3669002	donor_gain	0.9700
17:3669096–3669097	acceptor_loss	0.9700	6
17:3668900–3668901	donor_loss	0.9500	5
17:3668901	donor_loss	0.9400
17:3669013–3669014	donor_loss	0.9300	4
17:3669019	donor_gain	0.9300
17:3669013–3669014	donor_loss	0.9200	2
17:3668984	donor_gain	0.9100
17:3669012	donor_loss	0.9100

AlphaMissense

350 missense substitutions predicted likely pathogenic (of 681 scored), across 86 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N22	8	0.951	0.988
F102	8	0.943	0.986
H108	8	0.938	0.986
F78	8	0.883	0.980
F54	8	0.868	0.969
F52	8	0.865	0.964
W100	7	0.983	0.997
M106	7	0.882	0.987
F99	7	0.879	0.974
W74	7	0.851	0.967
F94	7	0.822	0.922
G38	6	0.991	0.999
G42	6	0.990	0.998
G51	6	0.982	0.996
G45	6	0.963	0.990
G105	6	0.958	0.996
V107	6	0.931	0.983
T101	6	0.900	0.982
T95	6	0.854	0.979
T31	6	0.726	0.797

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	1.44e-05

Disease associations

OMIM: gene MIM:620261 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	increases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1R4	Abcam HeLa EMC6 KO	Cancer cell line	Female
CVCL_SL93	HAP1 EMC6 (-) 1	Cancer cell line	Male
CVCL_SL94	HAP1 EMC6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.