ERMARD

Summary

ERMARD (ER membrane associated RNA degradation, HGNC:21056) is a protein-coding gene on chromosome 6q27, encoding Endoplasmic reticulum membrane-associated RNA degradation protein (Q5T6L9). May play a role in neuronal migration during embryonic development.

The protein encoded by this gene contains 2 transmembrane domains near the C-terminus and is localized in the endoplasmic reticulum. Knockout of this gene in developing rat brain showed that it may be involved in neuronal migration. Mutations in this gene are associated with periventricular nodular heterotopia-6 (PVNH6). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 55780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): periventricular nodular heterotopia (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 378 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 68
• MANE Select transcript: NM_018341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21056
Approved symbol	ERMARD
Name	ER membrane associated RNA degradation
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11152, dJ266L20.3
Ensembl gene	ENSG00000130023
Ensembl biotype	protein_coding
OMIM	615532
Entrez	55780

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000366771, ENST00000366772, ENST00000366773, ENST00000392095, ENST00000418781, ENST00000477995, ENST00000492738, ENST00000586341, ENST00000588437, ENST00000588451, ENST00000590017, ENST00000590711, ENST00000592315, ENST00000592367, ENST00000592580, ENST00000592745, ENST00000854211, ENST00000854212, ENST00000854213, ENST00000940706, ENST00000940707, ENST00000971714, ENST00000971715

RefSeq mRNA: 5 — MANE Select: NM_018341 NM_001278531, NM_001278532, NM_001278533, NM_001410957, NM_018341

CCDS: CCDS34576, CCDS64572, CCDS64573, CCDS64574, CCDS94040

Canonical transcript exons

ENST00000366773 — 18 exons

Exon	Start	End
ENSE00000893143	169759838	169759974
ENSE00000893144	169760642	169760756
ENSE00000893147	169762429	169762531
ENSE00000893148	169768103	169768171
ENSE00001010164	169766638	169766667
ENSE00003493356	169753864	169754032
ENSE00003520010	169779182	169779295
ENSE00003542039	169756719	169756808
ENSE00003572476	169756338	169756439
ENSE00003603481	169755283	169755422
ENSE00003619222	169775270	169775346
ENSE00003631556	169776455	169776673
ENSE00003645476	169769540	169769713
ENSE00003658349	169775940	169776065
ENSE00003669493	169773319	169773402
ENSE00003672908	169758968	169759065
ENSE00003685225	169751622	169751663
ENSE00003848515	169781330	169781600

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5729 / max 61.1785, expressed in 1748 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71276	6.4872	1747
71277	0.0857	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.75	gold quality
right testis	UBERON:0004534	94.74	gold quality
left testis	UBERON:0004533	94.56	gold quality
endometrium	UBERON:0001295	94.19	gold quality
testis	UBERON:0000473	94.05	gold quality
left ovary	UBERON:0002119	93.51	gold quality
right ovary	UBERON:0002118	93.44	gold quality
metanephros cortex	UBERON:0010533	93.35	gold quality
ovary	UBERON:0000992	93.33	gold quality
corpus callosum	UBERON:0002336	93.15	gold quality
pituitary gland	UBERON:0000007	92.86	gold quality
right lobe of liver	UBERON:0001114	92.83	gold quality
spleen	UBERON:0002106	92.78	gold quality
tibial nerve	UBERON:0001323	92.64	gold quality
adenohypophysis	UBERON:0002196	92.31	gold quality
calcaneal tendon	UBERON:0003701	92.24	gold quality
right lobe of thyroid gland	UBERON:0001119	92.20	gold quality
right adrenal gland cortex	UBERON:0035827	92.09	gold quality
right adrenal gland	UBERON:0001233	91.98	gold quality
cortex of kidney	UBERON:0001225	91.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.90	gold quality
body of uterus	UBERON:0009853	91.84	gold quality
mucosa of stomach	UBERON:0001199	91.78	gold quality
thyroid gland	UBERON:0002046	91.71	gold quality
granulocyte	CL:0000094	91.69	gold quality
left lobe of thyroid gland	UBERON:0001120	91.66	gold quality
fallopian tube	UBERON:0003889	91.54	gold quality
skin of abdomen	UBERON:0001416	91.49	gold quality
lymph node	UBERON:0000029	91.39	gold quality
zone of skin	UBERON:0000014	91.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	79.09
E-ANND-3	yes	3.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• C6orf70 plays a major role in the control of neuronal migration; its haploinsufficiency or mutation causes periventricular nodular heterotopia. (PMID:24056535)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ermard	ENSMUSG00000036552
mus_musculus	Ermardl1	ENSMUSG00000116895
mus_musculus	Ermardl2	ENSMUSG00000116953
rattus_norvegicus	Ermard	ENSRNOG00000015230

Protein

Protein identifiers

Endoplasmic reticulum membrane-associated RNA degradation protein — Q5T6L9 (reviewed: Q5T6L9)

All UniProt accessions (8): Q5T6L9, K7EM31, K7EME8, K7EMW5, K7EPX8, K7ER62, K7ERF7, K7ESI0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neuronal migration during embryonic development.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Periventricular nodular heterotopia 6 (PVNH6) [MIM:615544] A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH6 results in delayed psychomotor development, delayed speech, strabismus, and onset of seizures with hypsarrhythmia in early infancy. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5T6L9-1	1	yes
Q5T6L9-2	2
Q5T6L9-3	3
Q5T6L9-4	4

RefSeq proteins (5): NP_001265460, NP_001265461, NP_001265462, NP_001397886, NP_060811* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025209	EMARD_N	Domain
IPR039635	ERMARD	Family

Pfam: PF13910

UniProt features (9 total): splice variant 3, transmembrane region 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T6L9-F1	90.79	0.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 212 (showing top): chr6q27, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, NUYTTEN_EZH2_TARGETS_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, CEBPZ_TARGET_GENES, LMTK3_TARGET_GENES, PAX3_TARGET_GENES, SRSF9_TARGET_GENES, ZNF146_TARGET_GENES, ZNF711_TARGET_GENES

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERMARD	ARFGEF2	Q9Y6D5	729
ERMARD	PHF10	Q8WUB8	610
ERMARD	TMTC3	Q6ZXV5	524
ERMARD	DCHS1	Q96JQ0	521
ERMARD	FAT4	Q6V0I7	510
ERMARD	DHRSX	Q8N5I4	507
ERMARD	INTS8	Q75QN2	507
ERMARD	FAM120B	Q96EK7	479
ERMARD	DYNLT2	Q8IZS6	477
ERMARD	Q12799	Q12799	465
ERMARD	PSMB1	P20618	464
ERMARD	EML1	O00423	448
ERMARD	RAB7B	Q96AH8	447
ERMARD	FLNA	P21333	442
ERMARD	WDR27	A2RRH5	440

IntAct

0 interactions, top by confidence:

BioGRID (2): ERMARD (Affinity Capture-RNA), ERMARD (Affinity Capture-RNA)

ESM2 similar proteins: A4IIK1, C6FG12, E7FH61, F5HEZ4, F6R2G2, F6S215, P30429, Q01001, Q01044, Q07440, Q16548, Q1L8H0, Q1LVQ2, Q20CR4, Q29IM7, Q32NG6, Q3C2I0, Q3MHH2, Q4R6F2, Q4V9P9, Q4VSN5, Q56P42, Q5RB52, Q5RBY8, Q5T6L9, Q5TBC7, Q5U228, Q60Z52, Q66674, Q6DFV1, Q6NU22, Q6NU51, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZN28, Q7KLI1, Q86XI2, Q8AXQ3, Q8IRY7

Diamond homologs: Q3B8R1, Q4R6F2, Q5T6L9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	193
Likely benign	104
Benign	53

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
88869	NM_018341.3(ERMARD):c.1130T>A (p.Ile377Asn)	Pathogenic
1696356	NM_018341.3(ERMARD):c.605+1G>A	Likely pathogenic
2429374	NM_018341.3(ERMARD):c.277C>T (p.Arg93Ter)	Likely pathogenic
3068306	NM_018341.3(ERMARD):c.1395-1G>T	Likely pathogenic

SpliceAI

3146 predictions. Top by Δscore:

Variant	Effect	Δscore
6:169758960:C:CA	acceptor_gain	1.0000
6:169758961:G:A	acceptor_gain	1.0000
6:169759003:T:TA	acceptor_gain	1.0000
6:169759834:CTAG:C	acceptor_loss	1.0000
6:169759835:TAGAT:T	acceptor_loss	1.0000
6:169759836:A:AG	acceptor_gain	1.0000
6:169759836:AGATA:A	acceptor_loss	1.0000
6:169759837:G:A	acceptor_loss	1.0000
6:169759837:G:GG	acceptor_gain	1.0000
6:169759837:GATA:G	acceptor_gain	1.0000
6:169759970:TCCTG:T	donor_gain	1.0000
6:169759971:CCTG:C	donor_gain	1.0000
6:169759972:CTG:C	donor_gain	1.0000
6:169759972:CTGG:C	donor_loss	1.0000
6:169759973:TG:T	donor_gain	1.0000
6:169759973:TGG:T	donor_loss	1.0000
6:169759974:GG:G	donor_gain	1.0000
6:169759974:GGTA:G	donor_loss	1.0000
6:169759975:G:GG	donor_gain	1.0000
6:169759975:GTAA:G	donor_loss	1.0000
6:169759976:T:A	donor_loss	1.0000
6:169762423:TCATA:T	acceptor_loss	1.0000
6:169762424:CATA:C	acceptor_loss	1.0000
6:169762425:A:AG	acceptor_gain	1.0000
6:169762425:ATAG:A	acceptor_gain	1.0000
6:169762425:ATAGG:A	acceptor_loss	1.0000
6:169762426:T:G	acceptor_gain	1.0000
6:169762426:TAG:T	acceptor_loss	1.0000
6:169762427:A:AG	acceptor_gain	1.0000
6:169762428:G:A	acceptor_loss	1.0000

AlphaMissense

4430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:169759028:T:A	W190R	0.992
6:169759028:T:C	W190R	0.992
6:169781397:T:A	W641R	0.992
6:169781397:T:C	W641R	0.992
6:169759037:T:C	F193L	0.991
6:169759039:T:A	F193L	0.991
6:169759039:T:G	F193L	0.991
6:169769597:A:C	S373R	0.991
6:169769599:C:A	S373R	0.991
6:169769599:C:G	S373R	0.991
6:169755405:T:A	W100R	0.987
6:169755405:T:C	W100R	0.987
6:169762476:T:C	L302P	0.985
6:169762480:G:C	R303S	0.983
6:169762480:G:T	R303S	0.983
6:169753993:T:A	W46R	0.982
6:169753993:T:C	W46R	0.982
6:169759016:C:A	R186S	0.982
6:169762487:T:C	F306L	0.982
6:169762489:T:A	F306L	0.982
6:169762489:T:G	F306L	0.982
6:169781399:G:C	W641C	0.982
6:169781399:G:T	W641C	0.982
6:169769587:A:C	R369S	0.981
6:169769587:A:T	R369S	0.981
6:169762464:T:C	L298P	0.980
6:169769552:G:C	D358H	0.979
6:169756765:T:C	L155P	0.978
6:169759038:T:C	F193S	0.977
6:169769586:G:C	R369T	0.977

dbSNP variants (sampled 300 via entrez): RS1000135718 (6:169751822 C>G,T), RS1000216511 (6:169763845 A>G), RS1000260380 (6:169767306 A>G), RS1000322016 (6:169781153 T>G), RS1000396256 (6:169775372 G>A), RS1000420338 (6:169750660 G>A), RS1000426095 (6:169775706 C>T), RS1000444200 (6:169769669 C>G), RS1000564324 (6:169770046 C>T), RS1000605900 (6:169766133 C>T), RS1000724633 (6:169761032 C>T), RS1000916919 (6:169777163 G>T), RS1001010120 (6:169777551 T>C), RS1001095407 (6:169759076 A>G), RS1001126698 (6:169771938 G>A)

Disease associations

OMIM: gene MIM:615532 | disease phenotypes: MIM:615544

GenCC curated gene-disease

Disease	Classification	Inheritance
periventricular nodular heterotopia	Supportive	Autosomal dominant
periventricular nodular heterotopia 6	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
periventricular nodular heterotopia	Limited	AD

Mondo (2): periventricular nodular heterotopia 6 (MONDO:0014240), periventricular nodular heterotopia (MONDO:0020341)

Orphanet (1): Nodular neuronal heterotopia (Orphanet:2149)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000771	Gynecomastia
HP:0000962	Hyperkeratosis
HP:0000963	Thin skin
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001310	Dysmetria
HP:0001321	Cerebellar hypoplasia
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001513	Obesity
HP:0001643	Patent ductus arteriosus
HP:0001654	Abnormal heart valve morphology
HP:0001659	Aortic regurgitation
HP:0001741	Phimosis

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D054091	Periventricular Nodular Heterotopia	C10.500.507.450.750; C16.131.666.507.450.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.