STEEP1

protein-coding

STING1 ER exit protein 1, the group of Spliceosomal P complex|Spliceosomal C complex

Gene summary

While this gene is well-supported by transcript data, no functional information on its protein products is currently available. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

Previous symbols:

CXorf56

MANE transcript

NM_022101.4

Inheritance

ClinVar variants

P:4U:63B:4

Top phenotype

Intellectual developmental disorder, X-linked, 107

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:119,538,149-119,565,409

External References & Databases

Ensembl (ENSG00000018610)

Transcript & Mutation Effects

hg38 • Region Span ~27.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked 107LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0049222

Submitter: Ambry Genetics

intellectual developmental disorder, X-linked 107MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0049222

Submitter: ClinGen

*STEEP1* is located on the X chromosome at Xq24 and encodes the STING1 ER exit protein 1. The encoded protein is thought to be essential in transport of the STING protein from the golgi to the endoplasmic reticulum. *STEEP1* was first reported in relation to X-linked intellectual disability in 2018 (Verkerk et al., PMID: 29374277). This condition is characterized by intellectual disability, global developmental delay (including in speech and motor development), characteristic facial features (such as elongated face and large/prominent ears), ADHD, tremors, and gait difficulties. 5 variants (small in-frame deletion, large deletion, 2 x frameshift, nonsense) that have been reported in at least 5 probands in 3 publications (PMIDs: 29374277, 31822863, 37495270) and ClinVar (SCV004099241, Greenwood Genetic Center) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (expression-level data) . The gene is shown to be expressed in hippocampal neurons (PMID: 29374277). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date 10/28/2025 (SOP Version 11).

X-linked syndromic intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0020119

Submitter: Illumina

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked, 107XL

Manifestation: Craniofacial; 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: 29374277

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STEEP1 variants in ClinVar

2 Conditions Cataloged

not providedTotal: 14

Intellectual disability, X-linked 107Total: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022101.4. 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			9 clinvar	3 clinvar		12
missense			35 clinvar	1 clinvar		36
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)			15 clinvar			15
Total	2	2	63	4	0	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022101.4	RefSeq	NP_071384.1	7	MANE Select
ENST00000644802.2	Ensembl	ENSP00000494123.2	7	MANE Select
NM_001170569.1	RefSeq	NP_001164040.1	6	Standard
NM_001170570.2	RefSeq	NP_001164041.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

nucleus
cytoplasm
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371594
Coding exons: 7
Length: 27286
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.24	30	89.6	0.335	0.00000692	1462
Missense (PolyPhen)		4	26.477	0.15107		451
Synonymous	1.53	21	32.0	0.655	0.00000233	396
Loss of Function	2.86	0	9.55	0.00	7.60e-7	160

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Mental retardation, X-linked 107 (MRX107) [MIM:301013]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:29374277}. Note=The disease is caused by mutations affecting the gene represented in this entry. The disease-causing mutation has been identified in one large family as a 2 base pair insertion in CXorf56 exon 2. This variant produces a premature stop codon, leading to nonsense-mediated mRNA decay. {ECO:0000269|PubMed:29374277}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

RVIS EVS: 0.04
RVIS percentile EVS: 56.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E

Gene Damage Prediction

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