IFRD1

protein-coding

interferon related developmental regulator 1, the group of Armadillo like helical domain containing

Gene summary

This gene is an immediate early gene that encodes a protein related to interferon-gamma. This protein may function as a transcriptional co-activator/repressor that controls the growth and differentiation of specific cell types during embryonic development and tissue regeneration. Mutations in this gene are associated with sensory/motor neuropathy with ataxia. This gene may also be involved in modulating the pathogenesis of cystic fibrosis lung disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

MANE transcript

NM_001550.4

Inheritance

ClinVar variants

U:69B:7

Top phenotype

spinocerebellar ataxia type 18

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr7:112,422,887-112,481,017

External References & Databases

Ensembl (ENSG00000006652)

Transcript & Mutation Effects

hg38 • Region Span ~58.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019064

Submitter: PanelApp Australia

spinocerebellar ataxia type 18SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011834

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFRD1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 8

IFRD1-related disorderTotal: 3

Charcot-Marie-Tooth diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001550.4. 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			3 clinvar	1 clinvar	3 clinvar	7
missense			62 clinvar	2 clinvar	1 clinvar	65
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	69	3	4	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001550.4	RefSeq	NP_001541.2	12	MANE Select
ENST00000403825.8	Ensembl	ENSP00000384477.3	12	MANE Select
NM_001007245.3	RefSeq	NP_001007246.1	12	Standard
NM_001197079.2	RefSeq	NP_001184008.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Hypertrophy Model

Biological Process

myoblast fate determination
striated muscle tissue development
negative regulation of axon extension
muscle cell differentiation
skeletal muscle tissue regeneration

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403825
Coding exons: 12
Length: 58050
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.26	191	247	0.774	0.0000129	2967
Missense (PolyPhen)		61	83.014	0.73481		1124
Synonymous	0.539	79	85.3	0.926	0.00000426	850
Loss of Function	2.74	9	23.3	0.386	0.00000119	301

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000033	0.000033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could play a role in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF. May be an autocrine factor that attenuates or amplifies the initial ligand-induced signal (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.490
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.967

Gene Damage Prediction

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