ERC1

Summary

ERC1 (ELKS/RAB6-interacting/CAST family member 1, HGNC:17072) is a protein-coding gene on chromosome 12p13.33, encoding ELKS/Rab6-interacting/CAST family member 1 (Q8IUD2). Regulatory subunit of the IKK complex.

The protein encoded by this gene is a member of a family of RIM-binding proteins. RIMs are active zone proteins that regulate neurotransmitter release. This gene has been found fused to the receptor-type tyrosine kinase gene RET by gene rearrangement due to the translocation t(10;12)(q11;p13) in thyroid papillary carcinoma. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23085 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 202 total — 1 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_178040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17072
Approved symbol	ERC1
Name	ELKS/RAB6-interacting/CAST family member 1
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	ELKS, KIAA1081, CAST2, MGC12974
Ensembl gene	ENSG00000082805
Ensembl biotype	protein_coding
OMIM	607127
Entrez	23085

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 32 protein_coding, 7 protein_coding_CDS_not_defined, 7 retained_intron, 6 nonsense_mediated_decay

ENST00000347735, ENST00000355446, ENST00000360905, ENST00000397203, ENST00000440394, ENST00000515210, ENST00000536573, ENST00000538971, ENST00000539007, ENST00000539802, ENST00000541503, ENST00000542302, ENST00000543086, ENST00000543151, ENST00000543263, ENST00000544277, ENST00000545318, ENST00000545948, ENST00000546231, ENST00000588412, ENST00000589028, ENST00000589132, ENST00000592048, ENST00000611180, ENST00000686476, ENST00000688324, ENST00000689995, ENST00000690222, ENST00000690948, ENST00000691018, ENST00000691140, ENST00000691177, ENST00000692909, ENST00000895621, ENST00000895622, ENST00000895623, ENST00000895624, ENST00000895625, ENST00000895626, ENST00000895627, ENST00000895628, ENST00000895629, ENST00000895630, ENST00000895631, ENST00000916652, ENST00000916653, ENST00000916654, ENST00000950324, ENST00000950325, ENST00000950326, ENST00000950327, ENST00000950328

RefSeq mRNA: 3 — MANE Select: NM_178040 NM_001301248, NM_178039, NM_178040

CCDS: CCDS53732, CCDS76504, CCDS8508

Canonical transcript exons

ENST00000360905 — 19 exons

Exon	Start	End
ENSE00001100229	1083164	1083580
ENSE00001318114	1027748	1028572
ENSE00002267005	991223	991322
ENSE00003470415	1181925	1182065
ENSE00003472540	1408149	1408247
ENSE00003492606	1263034	1263165
ENSE00003494710	1104750	1104824
ENSE00003506576	1189859	1190052
ENSE00003511191	1236769	1236904
ENSE00003517406	1110192	1110347
ENSE00003523832	1183281	1183421
ENSE00003550021	1141620	1141787
ENSE00003553686	1289852	1290012
ENSE00003586174	1490093	1495931
ENSE00003605237	1444562	1444750
ENSE00003634782	1112215	1112298
ENSE00003656936	1180540	1180677
ENSE00003686156	1371833	1371977
ENSE00003785663	1115866	1116033

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 97.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2244 / max 189.8109, expressed in 1771 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123342	9.1065	1751
123343	1.3459	820
123344	1.2751	682
123348	0.8839	126
123345	0.5747	281
123347	0.0383	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.80	gold quality
colonic epithelium	UBERON:0000397	96.38	gold quality
cortical plate	UBERON:0005343	95.78	gold quality
calcaneal tendon	UBERON:0003701	95.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.98	gold quality
cerebellar vermis	UBERON:0004720	91.47	gold quality
adrenal tissue	UBERON:0018303	91.20	gold quality
tendon	UBERON:0000043	90.38	gold quality
saphenous vein	UBERON:0007318	89.31	gold quality
stromal cell of endometrium	CL:0002255	88.90	gold quality
ganglionic eminence	UBERON:0004023	88.32	gold quality
cerebellar cortex	UBERON:0002129	88.03	gold quality
cerebellar hemisphere	UBERON:0002245	87.88	gold quality
cerebellum	UBERON:0002037	87.85	gold quality
corpus callosum	UBERON:0002336	87.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.91	gold quality
islet of Langerhans	UBERON:0000006	86.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.79	gold quality
popliteal artery	UBERON:0002250	85.56	gold quality
tibial artery	UBERON:0007610	85.54	gold quality
synovial joint	UBERON:0002217	85.45	gold quality
ventricular zone	UBERON:0003053	84.94	gold quality
aorta	UBERON:0000947	84.64	gold quality
lower esophagus	UBERON:0013473	84.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.37	gold quality
tonsil	UBERON:0002372	84.20	gold quality
lower lobe of lung	UBERON:0008949	84.00	gold quality
descending thoracic aorta	UBERON:0002345	83.91	gold quality
thoracic aorta	UBERON:0001515	83.44	gold quality
adrenal gland	UBERON:0002369	83.36	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	65.58
E-HCAD-25	yes	35.94
E-CURD-119	yes	29.05
E-ANND-3	yes	6.58
E-MTAB-10137	no	506.34
E-CURD-10	no	245.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKBIA, NFKBID

Literature-anchored findings (GeneRIF, showing 15)

• Analysis of the gene structure of four isoforms (ELKS beta, ELKS gamma, ELKS delta, and ELKS epsilon) in a case of papillary thyroid carcinoma reveal that the isoforms are produced by alternative splicing. (PMID:12203787)
• In vitro results indicate that ERC2/CAST, an active zone-specific isoform, interacts with all of the known isoforms of liprin-alpha and that liprin-alpha1 associates with both ERC2 and ERC1b (PMID:12923177)
• ELKS likely functions by recruiting IkappaBalpha to the IkappaB kinase (IKK) complex and thus serves a regulatory function for IKK activation (PMID:15218148)
• ERC1-PDGFRB fusion is associated with acute myeloid leukemia (PMID:17690697)
• ATM- and NEMO-dependent ubiquitination of ELKS leads to the ubiquitin-dependent assembly of TAK1/TAB2/3 and NEMO/IKK complexes, resulting in IKK and NF-kappaB activation following genotoxic stimuli. (PMID:20932476)
• a new, but rare, antigen in Lambert-Eaton myasthenic syndrome (PMID:23583364)
• Liprin-alpha1, ERC1a and LL5 also define new highly polarized and dynamic cytoplasmic structures uniquely localized near the protruding cell edge (PMID:24982445)
• ELKS removal has differential, synapse-specific effects on readily releasable vesicles and probability of release, and findings establish important roles for ELKS N-terminal domains in synaptic vesicle priming. (PMID:27253063)
• The results indicate that liprin-alpha1, LL5 and ERC1 define a novel dynamic membrane-less compartment that regulates matrix degradation by affecting invadosome motility. (PMID:29348417)
• Several studies had established that ELKS is a redundant scaffold at the active zone, and that disruption of this scaffold impairs fusion of synaptic vesicles. In non-neuronal cells, scaffolding and exocytotic functions of ELKS seem to be important for constitutive secretion of other cargo. [review] (PMID:29491150)
• Knockdown of ERC1, RAB4B, COPA, and COPB2, caused profound loss of virus production. (PMID:29946045)
• The ELKS forms a potent insulin secretion complex with L-type voltage-dependent Ca(2+) channels on the vascular-facing plasma membrane of beta-cells, enabling polarized Ca(2+) influx and first-phase insulin secretion from islets. (PMID:31500835)
• Volumetric GWAS of medial temporal lobe structures identifies an ERC1 locus using ADNI high-resolution T2-weighted MRI data. (PMID:32768867)
• Oligomerized liprin-alpha promotes phase separation of ELKS for compartmentalization of presynaptic active zone proteins. (PMID:33761347)
• Interfering with the ERC1-LL5beta interaction disrupts plasma membrane-Associated platforms and affects tumor cell motility. (PMID:37437062)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	erc1a	ENSDARG00000009941
danio_rerio	erc1b	ENSDARG00000031930
danio_rerio	ERC1	ENSDARG00000076014
mus_musculus	Erc1	ENSMUSG00000030172
rattus_norvegicus	Erc1	ENSRNOG00000009264
caenorhabditis_elegans		WBGENE00018330

Paralogs (1): ERC2 (ENSG00000187672)

Protein

Protein identifiers

ELKS/Rab6-interacting/CAST family member 1 — Q8IUD2 (reviewed: Q8IUD2)

Alternative names: Rab6-interacting protein 2

All UniProt accessions (13): Q8IUD2, A0A8I5KS52, A0A8I5KT07, A0A8I5QKW1, A0A8J9C065, G8JLD3, K7EIZ7, K7EKH8, K7EP25, K7EPD6, K7EPP6, X6RLX0, X6RM00

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport.

Subunit / interactions. Part of a complex with CHUK, IKBKB and IKBKG. Interacts with CHUK, IKBKB and IKBKG. The interaction with IKBKG is independent of CHUK and IKBKB. Interacts with NFKBIA. Isoform 4 interacts with PPFIA1, and through its C-terminus with the PDZ domains of RIMS1 and RIMS2. Interacts with ERC2/CAST1. Interacts with the GTB-bound forms of RAB6A isoform 1 and isoform 2 and with RAB6B. The interaction was strongest with RAB6B, followed by RAB6A isoform 2 and weakest with RAB6A isoform 1. Interacts with SDCCAG8. Part of a cortical microtubule stabilization complex (CMSC) composed of KANK1, PPFIA1, PPFIBP1, ERC1/ELKS, PHLDB2/LL5beta, CLASPs, KIF21A and possibly additional interactors; within CMSCs KANK1 and PHLDB2/LL5beta appear to be the core components for targeting of microtubule-binding proteins KIF21A and CLASPs, whereas PPFIA1, PPFIBP1 and ERC1/ELKS serve as scaffolds for protein clustering. Interacts (via N-terminus) with SRPK1 (via kinase domain) and SRPK2 (via kinase domain); the interaction is direct and may be involved in SRPK protein localization.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Membrane. Golgi apparatus membrane. Presynaptic cell membrane. Cell projection. Podosome.

Tissue specificity. Widely expressed. Isoform 2 and isoform 4 are abundantly expressed in brain. Isoform 1 and isoform 3 are predominantly expressed in testis and thyroid, and isoform 1 predominates in other tissues tested.

Post-translational modifications. Phosphorylated in an N-terminal region by SRPK1 and/or SRPK2.

Disease relevance. A chromosomal aberration involving ERC1/RAB6IP2 is found in papillary thyroid carcinomas (PTCs). Translocation t(10;12)(q11;p13) involving RET. In vitro, isoform 1, isoform 3 and isoform 5 participating in a ERC1-RET fusion protein activate tyrosine-protein kinase activity.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IUD2-1	1, ELKS epsilon	yes
Q8IUD2-2	2, ELKS beta
Q8IUD2-3	3, ELKS delta
Q8IUD2-4	4, ELKS alpha
Q8IUD2-5	5, ELKS gamma

RefSeq proteins (3): NP_001288177, NP_829883, NP_829884* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019018	Rab-bd_FIP-RBD	Domain
IPR019323	ELKS/CAST	Family
IPR037245	FIP-RBD_C_sf	Homologous_superfamily

Pfam: PF09457, PF10174

UniProt features (33 total): modified residue 10, splice variant 6, sequence conflict 4, region of interest 3, compositionally biased region 3, sequence variant 2, coiled-coil region 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUD2-F1	75.64	0.31

Functional residue map

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

Catalytic / active sites (1): 719–720 (breakpoint for translocation to form erc1-ret oncogene)

Post-translational modifications (10): 10, 17, 21, 37, 38, 55, 75, 94, 1005, 1046

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 277 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RRAGTTGT_UNKNOWN, MORF_MSH3, MORF_BRCA1, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MORF_ATRX, PID_IL1_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CELLULAR_COMPONENT_MAINTENANCE, CREBP1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, MORF_ESR1

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), I-kappaB phosphorylation (GO:0007252), protein transport (GO:0015031), retrograde transport, endosome to Golgi (GO:0042147), maintenance of presynaptic active zone structure (GO:0048790), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092)

GO Molecular Function (5): PDZ domain binding (GO:0030165), small GTPase binding (GO:0031267), cadherin binding (GO:0045296), structural constituent of presynaptic active zone (GO:0098882), protein binding (GO:0005515)

GO Cellular Component (16): Golgi membrane (GO:0000139), podosome (GO:0002102), cytoplasm (GO:0005737), centrosome (GO:0005813), IkappaB kinase complex (GO:0008385), ciliary basal body (GO:0036064), presynaptic membrane (GO:0042734), synapse (GO:0045202), presynaptic active zone cytoplasmic component (GO:0098831), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
presynaptic active zone	2
microtubule organizing center	2
cell junction	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein phosphorylation	1
canonical NF-kappaB signal transduction	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
maintenance of synapse structure	1
presynaptic active zone organization	1
protein domain specific binding	1
GTPase binding	1
cell adhesion molecule binding	1
maintenance of presynaptic active zone structure	1
structural constituent of synapse	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
actin-based cell projection	1
intracellular anatomical structure	1
centriole	1
cytosol	1
serine/threonine protein kinase complex	1
cilium	1
synaptic membrane	1
presynapse	1
cell cortex region	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERC1	UNC13B	O14795	993
ERC1	CHUK	O15111	991
ERC1	PHLDB2	Q86SQ0	985
ERC1	PPFIA1	Q13136	984
ERC1	IKBKG	Q9Y6K9	984
ERC1	IKBKB	O14920	977
ERC1	RAB6A	P20340	964
ERC1	PPFIA3	O75145	957
ERC1	RIMS1	Q86UR5	942
ERC1	CLASRP	Q8N2M8	864
ERC1	KANK1	Q14678	810
ERC1	RIMS2	Q9UQ26	785
ERC1	UNC13A	Q9UPW8	760
ERC1	PPFIA2	O75334	701
ERC1	PPFIBP1	Q86W92	691

IntAct

179 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
ERC1	YWHAG	psi-mi:“MI:0915”(physical association)	0.850
CDK19	MED7	psi-mi:“MI:0914”(association)	0.800
CDK19	MED19	psi-mi:“MI:0914”(association)	0.770
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
KBTBD7	PLD2	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PARP2	ERC1	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
ERC1	RASSF8	psi-mi:“MI:0915”(physical association)	0.400
AKT2	ERC1	psi-mi:“MI:0915”(physical association)	0.400
	DENR	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
Ckap5	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Kif4	UMPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (255): ERC1 (Affinity Capture-MS), ADPRHL2 (Co-fractionation), SNX2 (Co-fractionation), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Biochemical Activity), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS), ERC1 (Proximity Label-MS)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z8P9, A6QR54, B4KE73, E9Q7G0, F1R4Y7, O15083, O55156, O60437, O61308, Q11102, Q13439, Q15643, Q3SWS9, Q5DTN8, Q5M9N0, Q5PQ23, Q5RI56, Q5U4E6, Q5VZ66, Q5ZKK5, Q66H89, Q6DFL0, Q6PH08, Q6ZU80, Q7ZW57, Q811U3, Q8BI22, Q8BVL9, Q8CDI6, Q8CDI7, Q8CGB3, Q8HYY4, Q8IUD2, Q8K3M6, Q8WXW3, Q91VW5, Q96AA8, Q96N16

Diamond homologs: O15083, Q6PH08, Q811U3, Q8IUD2, Q8K3M6, Q99MI1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ERC1	up-regulates	CHUK	binding
ERC1	up-regulates	IKK-complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 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
Activation of BAD and translocation to mitochondria	8	46.9×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	36.2×	2e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	31.0×	9e-07
Activation of BH3-only proteins	8	30.6×	7e-09
FOXO-mediated transcription	8	20.7×	2e-07
Intrinsic Pathway for Apoptosis	8	18.0×	4e-07
Loss of Nlp from mitotic centrosomes	13	15.9×	2e-10
Loss of proteins required for interphase microtubule organization from the centrosome	13	15.9×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of axon extension	5	14.5×	7e-03
protein targeting	6	12.5×	4e-03
intracellular protein localization	14	8.3×	2e-06
cilium assembly	12	5.0×	4e-03
intracellular signal transduction	16	3.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	152
Likely benign	11
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
872304	GRCh37/hg19 12p13.33(chr12:1136914-1599259)x1	Pathogenic
635768	GRCh37/hg19 12p13.33(chr12:1345909-1476210)x1	Likely pathogenic
804463	NM_178040.4(ERC1):c.3037dup (p.Leu1013fs)	Likely pathogenic

SpliceAI

7415 predictions. Top by Δscore:

Variant	Effect	Δscore
12:1028569:CCAGG:C	donor_loss	1.0000
12:1028570:CAGG:C	donor_loss	1.0000
12:1028572:GGTA:G	donor_loss	1.0000
12:1083155:T:A	acceptor_loss	1.0000
12:1083155:T:TA	acceptor_gain	1.0000
12:1083156:G:A	acceptor_gain	1.0000
12:1083162:A:AG	acceptor_gain	1.0000
12:1083162:AG:A	acceptor_loss	1.0000
12:1083163:G:GA	acceptor_gain	1.0000
12:1083163:GC:G	acceptor_gain	1.0000
12:1083163:GCA:G	acceptor_gain	1.0000
12:1083163:GCAC:G	acceptor_gain	1.0000
12:1083567:G:GG	donor_gain	1.0000
12:1083576:GAGAG:G	donor_gain	1.0000
12:1083577:AGAGG:A	donor_loss	1.0000
12:1083578:GAG:G	donor_gain	1.0000
12:1083581:G:GA	donor_loss	1.0000
12:1083582:T:A	donor_loss	1.0000
12:1104744:CTACA:C	acceptor_loss	1.0000
12:1104745:TACA:T	acceptor_loss	1.0000
12:1104747:CAG:C	acceptor_loss	1.0000
12:1104748:A:C	acceptor_loss	1.0000
12:1104749:GGA:G	acceptor_gain	1.0000
12:1104821:GAAG:G	donor_gain	1.0000
12:1104822:AAGGT:A	donor_loss	1.0000
12:1104823:AGGTA:A	donor_loss	1.0000
12:1104824:GGTA:G	donor_loss	1.0000
12:1104825:GTAA:G	donor_loss	1.0000
12:1104826:T:G	donor_loss	1.0000
12:1109742:G:GT	donor_gain	1.0000

AlphaMissense

7423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:1028468:T:C	F189L	1.000
12:1028469:T:C	F189S	1.000
12:1028469:T:G	F189C	1.000
12:1028470:C:A	F189L	1.000
12:1028470:C:G	F189L	1.000
12:1028471:T:A	W190R	1.000
12:1028471:T:C	W190R	1.000
12:1028473:G:C	W190C	1.000
12:1028473:G:T	W190C	1.000
12:1028474:A:C	S191R	1.000
12:1028476:C:A	S191R	1.000
12:1028476:C:G	S191R	1.000
12:1028484:T:C	L194P	1.000
12:1028488:G:C	K195N	1.000
12:1028488:G:T	K195N	1.000
12:1083189:T:C	L232P	1.000
12:1083345:T:C	L284P	1.000
12:1083375:G:C	R294P	1.000
12:1083399:T:C	L302P	1.000
12:1083408:G:C	R305P	1.000
12:1083416:T:C	S308P	1.000
12:1083429:T:C	L312P	1.000
12:1083432:T:C	L313P	1.000
12:1083509:G:C	A339P	1.000
12:1115939:T:C	L492P	1.000
12:1115989:T:C	S509P	1.000
12:1115998:G:C	A512P	1.000
12:1116013:G:C	A517P	1.000
12:1116023:T:C	L520P	1.000
12:1141626:G:C	A526P	1.000

dbSNP variants (sampled 300 via entrez): RS1000012234 (12:1091226 T>A,G), RS1000025135 (12:1430200 A>G,T), RS1000029342 (12:1178085 A>G), RS1000030847 (12:1097483 C>T), RS1000032394 (12:1156570 C>T), RS1000034059 (12:1071682 T>C), RS1000034546 (12:1059176 G>A), RS1000037783 (12:1043597 G>A), RS1000060236 (12:1469155 T>C), RS1000062835 (12:1169973 T>A), RS1000064727 (12:1017872 G>C,T), RS1000066123 (12:1462005 A>G), RS1000082437 (12:1091447 G>A), RS1000093432 (12:1170259 C>T), RS1000095492 (12:1017661 G>A)

Disease associations

OMIM: gene MIM:607127 | disease phenotypes: MIM:617011

GenCC curated gene-disease

Mondo (1): macrocephaly, dysmorphic facies, and psychomotor retardation (MONDO:0014863)

Orphanet (1): Megalencephaly-severe kyphoscoliosis-overgrowth syndrome (Orphanet:457359)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001482_30	Lumbar spine bone mineral density	6.000000e-12
GCST005908_40	Height	2.000000e-07
GCST005951_70	Body mass index	1.000000e-11
GCST006106_4	Forehead morphology	3.000000e-06
GCST010220_1	Attention deficit hyperactivity disorder (hyperactivity-impulsivity symptoms)	3.000000e-06
GCST011055_1	Medial temporal lobe substructure volumes	3.000000e-09
GCST012490_317	Femur bone mineral density x serum urate levels interaction	2.000000e-09
GCST012490_577	Femur bone mineral density x serum urate levels interaction	4.000000e-11
GCST90020025_656	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020027_1635	Waist-hip index	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004868	volumetric brain MRI
EFO:0004531	urate measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	7
Valproic Acid	increases expression, affects expression	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
geraniol	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
pinostrobin	increases expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7PJ	Ubigene A-549 ERC1 KO	Cancer cell line	Male
CVCL_D8L1	Ubigene HCT 116 ERC1 KO	Cancer cell line	Male
CVCL_D9EI	Ubigene HEK293 ERC1 KO	Transformed cell line	Female
CVCL_E0CT	Ubigene HeLa ERC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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