CSF2RA

colony stimulating factor 2 receptor subunit alpha, the group of Pseudoautosomal region 1|CD molecules

Basic information

Region (hg38): X:1268799-1310381

Previous symbols: [ "CSF2R" ]

Links

ENSG00000198223 ∙ NCBI:1438 ∙ OMIM:306250, 425000 ∙ HGNC:2435 ∙ Uniprot:P15509 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary pulmonary alveolar proteinosis (Supportive), mode of inheritance: AR
• surfactant metabolism dysfunction, pulmonary, 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Surfactant metabolism dysfunction, pulmonary, 4	XL	Pulmonary	The condition manifests with childhood-onset respiratory insufficiency due to pulmonary alveolar proteinosis , and treatment with whole-lung lavage has been reported as beneficial; It has additionally been reported that diagnosis has important therapeutic implications, as BMT/HSCT can be effective	Pulmonary	18955567; 18955570; 20622029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSF2RA gene.

• Surfactant metabolism dysfunction, pulmonary, 4 (298 variants)
• not provided (126 variants)
• not specified (20 variants)
• CSF2RA-related condition (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSF2RA gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	56	8	66
missense	1	1	134	13	10	159
nonsense	7	1				8
start loss						0
frameshift	5					5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			7	15		22
non coding			2	54	89	145
Total	13	5	139	123	107

Highest pathogenic variant AF is 0.0000399

Variants in CSF2RA

This is a list of pathogenic ClinVar variants found in the CSF2RA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-1282485-G-A			Benign (Sep 24, 2019)
X-1282541-A-G			Benign (Mar 31, 2019)
X-1282599-A-AT			Benign (Mar 31, 2019)
X-1282715-G-C		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Aug 14, 2023)
X-1282717-T-C		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Jun 04, 2022)
X-1282718-G-T		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Nov 21, 2023)
X-1282720-C-A		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (May 04, 2022)
X-1282723-G-A		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Dec 02, 2021)
X-1282724-C-A		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Jun 09, 2019)
X-1282728-C-T		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Apr 12, 2023)
X-1282730-G-A		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Jul 17, 2023)
X-1282738-A-G		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Dec 24, 2021)
X-1282746-C-T		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Mar 05, 2021)
X-1282753-C-G		not specified • Surfactant metabolism dysfunction, pulmonary, 4 • CSF2RA-related disorder	Benign (Feb 01, 2024)
X-1282760-C-T		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Feb 12, 2019)
X-1282772-G-T		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Sep 13, 2018)
X-1282777-C-T		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Nov 17, 2023)
X-1282778-G-A		Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (Aug 24, 2022)
X-1282786-A-G		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Jan 15, 2024)
X-1282790-A-G		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Oct 03, 2023)
X-1282793-C-T		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Sep 15, 2023)
X-1282796-G-A		Surfactant metabolism dysfunction, pulmonary, 4	Likely benign (Sep 06, 2022)
X-1282897-C-G			Likely benign (Feb 21, 2019)
X-1285484-G-A			Benign (Dec 31, 2018)
X-1285574-C-A			Benign (Dec 31, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSF2RA	protein_coding	protein_coding	ENST00000417535	12	41582

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.40e-10	0.444	124800	18	773	125591	0.00315

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.837	260	225	1.16	0.0000148	2826
Missense in Polyphen		74	66.05	1.1204		871
Synonymous	-3.40	133	91.6	1.45	0.00000680	816
Loss of Function	1.11	18	23.9	0.754	0.00000146	278

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0440	0.0437
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000217	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000265	0.000264
Middle Eastern	0.000217	0.000217
South Asian	0.000196	0.000196
Other	0.000816	0.000816

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Low affinity receptor for granulocyte-macrophage colony- stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
• Disease: DISEASE: Pulmonary surfactant metabolism dysfunction 4 (SMDP4) [MIM:300770]: A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid- Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. {ECO:0000269|PubMed:18955567, ECO:0000269|PubMed:18955570}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Signaling by GPCR;Signal Transduction;Signaling by Interleukins;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Surfactant metabolism;Metabolism of proteins;Immune System;Interleukin receptor SHC signaling;Interleukin-2 family signaling;JAK STAT MolecularVariation 2;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;GMCSF-mediated signaling events;Alpha9 beta1 integrin signaling events;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Intolerance Scores

• loftool: 0.0175
• rvis_EVS: 1
• rvis_percentile_EVS: 90.77

Haploinsufficiency Scores

• pHI: 0.237
• hipred: N
• hipred_score: 0.493
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.820

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Csf2ra

Gene ontology

• Biological process: MAPK cascade;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;cellular protein metabolic process
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;external side of plasma membrane;receptor complex
• Molecular function: protein tyrosine kinase activity;cytokine receptor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;cytokine binding;signaling receptor activity