AMFR

autocrine motility factor receptor, the group of Ring finger proteins

Basic information

Region (hg38): 16:56361452-56425545

Links

ENSG00000159461

∙ NCBI:267 ∙ OMIM:603243 ∙ HGNC:463 ∙ Uniprot:Q9UKV5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spastic paraplegia 89, autosomal recessive (Strong), mode of inheritance: AR
spastic paraplegia 89, autosomal recessive (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 89, autosomal recessive	AR	General	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	Neurologic	37119330

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMFR gene.

not_specified (67 variants)
Spastic_paraplegia_89,_autosomal_recessive (7 variants)
not_provided (3 variants)
Marfanoid_habitus_and_intellectual_disability (1 variants)
Breast_ductal_adenocarcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMFR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001144.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			67 clinvar	2 clinvar		69
nonsense	3 clinvar					3
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	5	1	67	3	0

Highest pathogenic variant AF is 0.00000657583

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMFR	protein_coding	protein_coding	ENST00000290649	14	64087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000584	1.00	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.87	267	368	0.726	0.0000229	4205
Missense in Polyphen		50	87.182	0.57351		881
Synonymous	1.30	118	137	0.859	0.00000894	1284
Loss of Function	3.20	13	32.8	0.396	0.00000183	354

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000832	0.000832
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000163	0.000163
South Asian	0.0000371	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97- AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97- AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. {ECO:0000269|PubMed:10456327, ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:24424410}.;
Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;ER Quality Control Compartment (ERQC);Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation;N-glycan trimming in the ER and Calnexin/Calreticulin cycle (Consensus)

Recessive Scores

pRec: 0.172

Intolerance Scores

loftool: 0.602
rvis_EVS: -1.09
rvis_percentile_EVS: 7.05

Haploinsufficiency Scores

pHI: 0.317
hipred: Y
hipred_score: 0.652
ghis: 0.609

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Amfr
Phenotype: liver/biliary system phenotype; neoplasm; immune system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: protein polyubiquitination;protein folding;ubiquitin-dependent protein catabolic process;signal transduction;aging;learning or memory;ubiquitin-dependent ERAD pathway;endoplasmic reticulum unfolded protein response;positive regulation of protein binding;protein complex oligomerization;protein autoubiquitination;protein K48-linked ubiquitination;endoplasmic reticulum mannose trimming
Cellular component: nucleus;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;dendrite;growth cone;protein-containing complex;Derlin-1 retrotranslocation complex;neuronal cell body;endoplasmic reticulum quality control compartment;perinuclear region of cytoplasm
Molecular function: ubiquitin-protein transferase activity;protein binding;protein binding, bridging;ubiquitin-ubiquitin ligase activity;signaling receptor activity;identical protein binding;metal ion binding;chaperone binding;ubiquitin protein ligase activity;BAT3 complex binding;ubiquitin-specific protease binding