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SF3B4 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SF3B4 gene

The SF3B4 gene provides instructions for the SAP49 protein, a component of the spliceosome complex essential for processing genetic blueprints and regulating bone and cartilage development.

Normal Function

The SF3B4 gene provides instructions for making the SAP49 protein, which is part of a complex called a spliceosome. Spliceosomes help process messenger RNA (mRNA), which serves as a genetic blueprint for making proteins. The spliceosomes recognize and then remove regions from mRNA molecules that are not used in the blueprint (introns).

The SAP49 protein may also be involved in a chemical signaling pathway known as the bone morphogenic protein (BMP) pathway. This signaling pathway regulates various cellular processes and is involved in the growth of cells. The SAP49 protein is particularly important for the maturation of cells that build bones and cartilage (osteoblasts and chondrocytes).

Health Conditions Related to Genetic Changes

Nager syndrome

More than 30 mutations in the SF3B4 gene have been found to cause Nager syndrome, which is primarily characterized by abnormalities of the face, hands, and arms, such as underdeveloped cheek bones (malar hypoplasia), a small lower jaw (micrognathia), and malformed or absent thumbs. More than half of people with this condition have a mutation in the SF3B4 gene. These mutations prevent the production of SAP49 protein or lead to production of a nonfunctional protein. Researchers suspect that problems with spliceosome formation may impair mRNA processing and alter the activity of genes involved in development, or that a loss of SAP49 may impair BMP pathway signaling, leading to abnormal bone development.

Other disorders

At least four SF3B4 gene mutations have been found to cause acrofacial dysostosis of Rodriguez, a severe disorder that causes underdevelopment of bones in the face, arms, and legs as well as lung abnormalities. Affected individuals often exhibit:

  • Phocomelia (hands located very close to the body due to short arm bones)
  • Missing fingers, toes, and fibula
  • Cleft palate
  • Microtia (small external ears)
  • Severe micrognathia (leading to life-threatening breathing problems)

Similar to Nager syndrome, researchers suspect that abnormal spliceosome function and disruption of the BMP signaling pathway impair normal bone development and limb formation in babies with this condition.

Other Names for This Gene

  • AFD1
  • Hsh49
  • pre-mRNA-splicing factor SF3b 49 kDa subunit
  • SAP 49
  • SAP49
  • SF3b49
  • SF3b50
  • spliceosomal protein
  • spliceosome-associated protein (U2 snRNP)
  • spliceosome-associated protein 49
  • splicing factor 3B subunit 4
  • splicing factor 3b, subunit 4, 49kD
  • splicing factor 3b, subunit 4, 49kDa

Frequently Asked Questions

blood or saliva sample is sent for genetic testing, typically using targeted gene panels or whole‑exome sequencing. The lab searches for pathogenic variants that either eliminate the SAP49 protein or produce a nonfunctional form. Results guide counseling and management.
Management is multidisciplinary. Surgical correction of cleft palate and jaw abnormalities may be needed to improve feeding and speech. Hand and arm anomalies can be addressed with orthopedic surgery or prosthetic devices. Early physical and occupational therapy helps with motor development, while speech therapy supports language skills. Regular monitoring for airway problems and feeding difficulties is essential.
Parents and doctors look for a combination of facial and limb anomalies: a small lower jaw (micrognathia), underdeveloped cheekbones (malar hypoplasia), a cleft palate, and missing or malformed thumbs and other fingers. The hands may show a “thumb‑like” appearance or absent thumbs, and the arms can be shortened. These features are usually evident at birth.
If the mutation is inherited, each pregnancy has a 50% chance of inheriting the abnormal gene. If the mutation is de novo, the recurrence risk is low but not zero. Prenatal testing (amniocentesis or chorionic villus sampling) can detect the mutation early in pregnancy, allowing families to make informed decisions.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.