SERPINA7

protein-coding

serpin family A member 7, the group of Serpin peptidase inhibitors

Gene summary

There are three proteins including thyroxine-binding globulin (TBG), transthyretin and albumin responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in the bloodstream. This gene encodes the major thyroid hormone transport protein, TBG, in serum. It belongs to the serpin family in genomics, but the protein has no inhibitory function like many other members of the serpin family. Mutations in this gene result in TGB deficiency, which has been classified as partial deficiency, complete deficiency, and excess, based on the level of serum TBG. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined.[provided by RefSeq, Jun 2012]

Previous symbols:

MANE transcript

NM_000354.6

Inheritance

ClinVar variants

P:6U:58B:11

Top phenotype

Thyroxine-binding globulin deficiency; Thyroxine-binding globulin excess

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chrX:106,032,435-106,038,727

External References & Databases

Ensembl (ENSG00000123561)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Thyroxine-binding globulin deficiency; Thyroxine-binding globulin excessXL

Manifestation: Endocrine

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: 8530630; 11600582; 11889160; 19415532

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SERPINA7 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 42

Thyroxine-binding globulin quantitative trait locusTotal: 14

not providedTotal: 12

SERPINA7-related disorderTotal: 4

Thyroxine-binding globulin deficiencyTotal: 2

Thyroxine-binding globulin deficiency, partialTotal: 2

Thyroxine-binding globulin, ChicagoTotal: 1

Thyroxine-binding globulin, slowTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000354.6. 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			1 clinvar		1 clinvar	2
missense	4 clinvar		48 clinvar	7 clinvar	3 clinvar	62
nonsense			1 clinvar			1
start loss						0
frameshift	2 clinvar		7 clinvar			9
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	6	0	58	7	4	75

Highest pathogenic variant AF is 0.0060269665

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000354.6	RefSeq	NP_000345.2	4	MANE Select
ENST00000372563.2	Ensembl	ENSP00000361644.1	4	MANE Select
ENST00000327674.8	Ensembl	ENSP00000329374.4	4	Standard
ENST00000907820.1	Ensembl	ENSP00000577879.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thyroid hormone synthesis - Homo sapiens (human)

Biological Process

negative regulation of endopeptidase activity
thyroid hormone transport

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular region
extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327674
Coding exons: 4
Length: 5533
Individuals with no LoFs: 125547
Homozygous LoFs: 2
Heterozygous LoFs: 10
Defined: 125559
p: 0.0000478

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.656	166	144	1.15	0.00000978	2745
Missense (PolyPhen)		45	43.927	1.0244		970
Synonymous	-1.93	73	54.8	1.33	0.00000385	811
Loss of Function	1.06	5	8.28	0.604	5.24e-7	172

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000036	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00029	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000061	0.000044	rare
South Asian	0.00016	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major thyroid hormone transport protein in serum.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.119
RVIS EVS: 0.99
RVIS percentile EVS: 90.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.162

Gene Damage Prediction

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