ERGIC1

protein-coding

endoplasmic reticulum-golgi intermediate compartment 1

Gene summary

This gene encodes a cycling membrane protein which is an endoplasmic reticulum-golgi intermediate compartment (ERGIC) protein which interacts with other members of this protein family to increase their turnover. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001031711.3

Inheritance

ClinVar variants

P:3U:34B:5

Top phenotype

Arthrogryposis multiplex congenita 2, neurogenic type

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr5:172,834,251-172,952,792

External References & Databases

Ensembl (ENSG00000113719)

Transcript & Mutation Effects

hg38 • Region Span ~118.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

arthrogryposis multiplex congenita 2, neurogenic typeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008823

Submitter: Labcorp Genetics (formerly Invitae)

arthrogryposis multiplex congenita 2, neurogenic typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008823

Submitter: Orphanet

arthrogryposis multiplex congenita 2, neurogenic typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008823

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Arthrogryposis multiplex congenita 2, neurogenic typeAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 5491443; 28317099

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ERGIC1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 4

ERGIC1-related disorderTotal: 4

Arthrogryposis multiplex congenita 2, neurogenic typeTotal: 4

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001031711.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	1 clinvar	6
missense	1 clinvar	1 clinvar	30 clinvar	1 clinvar		33
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	1	2	34	4	1	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001031711.3	RefSeq	NP_001026881.1	10	MANE Select
ENST00000393784.8	Ensembl	ENSP00000377374.3	10	MANE Select
ENST00000326654.7	Ensembl	ENSP00000325127.3	5	Standard
ENST00000326654.8	Ensembl	ENSP00000325127.3	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endoplasmic reticulum to Golgi vesicle-mediated transport
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum

Molecular Function

protein binding

Cellular Component

Golgi membrane
nucleoplasm
endoplasmic reticulum membrane
endoplasmic reticulum-Golgi intermediate compartment
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393784
Coding exons: 10
Length: 118411
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.45	128	183	0.698	0.0000115	1933
Missense (PolyPhen)		44	77.096	0.57072		789
Synonymous	1.03	70	81.9	0.855	0.00000638	540
Loss of Function	3.07	3	16.4	0.183	8.01e-7	187

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00065	0.00065	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible role in transport between endoplasmic reticulum and Golgi. {ECO:0000303|PubMed:15308636}.;
Disease: DISEASE: Arthrogryposis multiplex congenita, neurogenic type (AMCN) [MIM:208100]: A form of arthrogryposis multiplex congenita, a heterogeneous group of disorders characterized by multiple joint contractures resulting, in some cases, from reduced or absent fetal movements. AMCN is due to a neurogenic defect and is characterized by congenital immobility of the limbs with fixation of multiple joints, and muscle wasting. AMCN transmission pattern is consistent with autosomal recessive inheritance in several families. Penetrance may be incomplete in females. {ECO:0000269|PubMed:28317099}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.350
RVIS EVS: -0.36
RVIS percentile EVS: 28.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium